Computing NCA Parameters for Theophylline

Examples simplify understanding. Below is an example of how to use the theophylline dataset to generate NCA parameters.

Load the data

## It is always a good idea to look at the data
knitr::kable(head(datasets::Theoph))

Subject	Wt	Dose	Time	conc
1	79.6	4.02	0.00	0.74
1	79.6	4.02	0.25	2.84
1	79.6	4.02	0.57	6.57
1	79.6	4.02	1.12	10.50
1	79.6	4.02	2.02	9.66
1	79.6	4.02	3.82	8.58

The columns that we will be interested in for our analysis are conc, Time, and Subject in the concentration data set and Dose, Time, and Subject for the dosing data set. Note that Dose in the theophylline dataset is in mg/kg rather than mg; the parameters calculated below do not use the dose amount, but dose-dependent parameters (for example, clearance, volume of distribution, or dose-normalized parameters) would first require converting the dose to mg by multiplying by the subject’s body weight (Wt).

## By default it is groupedData; convert it to a data frame for use
conc_obj <- PKNCAconc(as.data.frame(datasets::Theoph), conc~Time|Subject)

## Dosing data needs to only have one row per dose, so subset for
## that first.
d_dose <- unique(datasets::Theoph[datasets::Theoph$Time == 0,
                                  c("Dose", "Time", "Subject")])
knitr::kable(d_dose,
             caption="Example dosing data extracted from theophylline data set")

Example dosing data extracted from theophylline data set
	Dose	Subject
1	4.02	1
12	4.40	2
23	4.53	3
34	4.40	4
45	5.86	5
56	4.00	6
67	4.95	7
78	4.53	8
89	3.10	9
100	5.50	10
111	4.92	11
122	5.30	12

dose_obj <- PKNCAdose(d_dose, Dose~Time|Subject)

Merge the Concentration and Dose

After loading the data, they must be combined to prepare for parameter calculation. Intervals for calculation will automatically be selected based on the single.dose.aucs setting in PKNCA.options

data_obj_automatic <- PKNCAdata(conc_obj, dose_obj)
knitr::kable(PKNCA.options("single.dose.aucs"))

start	end	auclast	auclast_se	auclast_df	aucall	aucall_se	aucall_df	aumclast	aumclast_se	aumclast_df	aumcall	aumcall_se	aumcall_df	aucint.last	aucint.all	aumcint.last	aumcint.all	aucivint.last	aucivint.all	aucivpbext.int.last	aucivpbext.int.all	aumcivint.last	aumcivint.all	c0	cmax	cmin	tmax	tmin	tlast	tfirst	clast.obs	cl.last	cl.all	cl.int.all	cl.int.last	cl.ivint.all	cl.ivint.last	mrt.last	mrt.all	mrt.int.all	mrt.int.last	mrt.iv.last	mrt.ivint.all	mrt.ivint.last	vss.last	vss.iv.last	vss.all	vss.int.all	vss.int.last	vss.ivint.all	vss.ivint.last	cav.last	cav.int.last	cav.int.all	cav.all	cav.ivint.last	cav.ivint.all	ctrough	cstart	ptr	tlag	deg.fluc	swing	ceoi	aucabove.predose.all	aucabove.trough.all	count.conc	count.conc.measured	totdose	volpk	ae	clr.last	clr.int.inf.pred	clr.int.inf.obs	clr.int.all	clr.int.last	clr.all	clr.inf.obs	clr.inf.pred	fe	ertlst	ermax	ertmax	erint	erlst	ratio.cmax	ratio.auclast	ratio.aucint.last	ratio.aucint.all	sparse_auclast	sparse_auc_se	sparse_auc_df	sparse_aumclast	sparse_aumc_se	sparse_aumc_df	time.above	aucivlast	aucivlast_se	aucivlast_df	aucivall	aucivall_se	aucivall_df	aucivpbext.last	aucivpbext.all	aumcivlast	aumcivlast_se	aumcivlast_df	aumcivall	aumcivall_se	aumcivall_df	half.life	r.squared	adj.r.squared	lambda.z.corrxy	lambda.z	lambda.z.time.first	lambda.z.time.last	lambda.z.n.points	clast.pred	span.ratio	tobit.residual	adj.tobit.residual	lambda.z.n.points.blq	thalf.eff.last	thalf.eff.int.all	thalf.eff.int.last	thalf.eff.all	thalf.eff.iv.last	thalf.eff.ivint.all	thalf.eff.ivint.last	kel.last	kel.iv.last	kel.all	kel.int.all	kel.int.last	kel.ivint.all	kel.ivint.last	cl.iv.all	cl.iv.last	cl.sparse.last	f.last	f.all	f.int.last	f.int.all	mrt.sparse.last	mrt.iv.all	vz.all	vz.int.all	vz.int.last	vz.iv.all	vz.iv.last	vz.ivint.all	vz.ivint.last	vz.last	vss.iv.all	vss.sparse.last	cav.iv.last	cav.iv.all	aucinf.obs	aucinf.obs_se	aucinf.obs_df	aucinf.pred	aumcinf.obs	aumcinf.obs_se	aumcinf.obs_df	aumcinf.pred	aucint.inf.obs	aucint.inf.pred	aumcint.inf.obs	aumcint.inf.pred	aucivint.inf.obs	aucivint.inf.pred	aucivinf.obs	aucivinf.obs_se	aucivinf.obs_df	aucivinf.pred	aucivpbext.inf.obs	aucivpbext.inf.pred	aumcivint.inf.pred	aumcivint.inf.obs	aumcivinf.obs	aumcivinf.obs_se	aumcivinf.obs_df	aumcivinf.pred	thalf.eff.iv.all	aucpext.inf.obs	aucpext.inf.pred	kel.iv.all	kel.sparse.last	cl.inf.obs	cl.inf.pred	cl.int.inf.obs	cl.int.inf.pred	cl.iv.inf.obs	cl.iv.inf.pred	cl.ivint.inf.pred	cl.ivint.inf.obs	f.inf.obs	f.inf.pred	f.int.inf.obs	f.int.inf.pred	mrt.inf.obs	mrt.inf.pred	mrt.int.inf.obs	mrt.int.inf.pred	mrt.iv.inf.obs	mrt.iv.inf.pred	mrt.ivint.inf.pred	mrt.ivint.inf.obs	mrt.md.inf.obs	mrt.md.inf.pred	mrt.ivmd.inf.obs	mrt.ivmd.inf.pred	vz.inf.obs	vz.inf.pred	vz.int.inf.obs	vz.int.inf.pred	vz.iv.inf.obs	vz.iv.inf.pred	vz.ivint.inf.pred	vz.ivint.inf.obs	vz.sparse.last	vss.inf.obs	vss.inf.pred	vss.iv.inf.obs	vss.iv.inf.pred	vss.md.inf.obs	vss.md.inf.pred	vss.ivmd.inf.obs	vss.ivmd.inf.pred	vss.int.inf.obs	vss.int.inf.pred	vss.ivint.inf.pred	vss.ivint.inf.obs	cav.int.inf.obs	cav.int.inf.pred	cav.ivint.inf.obs	cav.ivint.inf.pred	ratio.aucinf.obs	ratio.aucinf.pred	thalf.eff.inf.obs	thalf.eff.inf.pred	thalf.eff.int.inf.pred	thalf.eff.int.inf.obs	thalf.eff.iv.inf.obs	thalf.eff.iv.inf.pred	thalf.eff.ivint.inf.pred	thalf.eff.ivint.inf.obs	kel.inf.obs	kel.inf.pred	kel.iv.inf.obs	kel.iv.inf.pred	kel.int.inf.obs	kel.int.inf.pred	kel.ivint.inf.pred	kel.ivint.inf.obs	auclast.dn	aucall.dn	aucinf.obs.dn	aucinf.pred.dn	aumclast.dn	aumcall.dn	aumcinf.obs.dn	aumcinf.pred.dn	cmax.dn	cmin.dn	clast.obs.dn	clast.pred.dn	cav.last.dn	ctrough.dn	adj_tobit_residual	aucivpbextall	aucivpbextinf.obs	aucivpbextinf.pred	aucivpbextint.all	aucivpbextint.last	aucivpbextlast	aucpext.obs	aucpext.pred	cav	cav.dn	cl.iv.obs	cl.iv.pred	cl.obs	cl.pred	clr.obs	clr.pred	count_conc	count_conc_measured	f.int.obs	f.int.pred	f.obs	f.pred	kel.iv.obs	kel.iv.pred	kel.obs	kel.pred	lambda.z.n.points_blq	mrt.iv.obs	mrt.iv.pred	mrt.ivmd.obs	mrt.ivmd.pred	mrt.md.obs	mrt.md.pred	mrt.obs	mrt.pred	thalf.eff.iv.obs	thalf.eff.iv.pred	thalf.eff.obs	thalf.eff.pred	time_above	tobit_residual	vss.iv.obs	vss.iv.pred	vss.ivmd.obs	vss.ivmd.pred	vss.md.obs	vss.md.pred	vss.obs	vss.pred	vz.iv.obs	vz.iv.pred	vz.obs	vz.pred
0	24	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE
0	Inf	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE

knitr::kable(data_obj_automatic$intervals)

end	auclast	auclast_se	auclast_df	aucall	aucall_se	aucall_df	aumclast	aumclast_se	aumclast_df	aumcall	aumcall_se	aumcall_df	aucint.last	aucint.all	aumcint.last	aumcint.all	aucivint.last	aucivint.all	aucivpbext.int.last	aucivpbext.int.all	aumcivint.last	aumcivint.all	c0	cmax	cmin	tmax	tmin	tlast	tfirst	clast.obs	cl.last	cl.all	cl.int.all	cl.int.last	cl.ivint.all	cl.ivint.last	mrt.last	mrt.all	mrt.int.all	mrt.int.last	mrt.iv.last	mrt.ivint.all	mrt.ivint.last	vss.last	vss.iv.last	vss.all	vss.int.all	vss.int.last	vss.ivint.all	vss.ivint.last	cav.last	cav.int.last	cav.int.all	cav.all	cav.ivint.last	cav.ivint.all	ctrough	cstart	ptr	tlag	deg.fluc	swing	ceoi	aucabove.predose.all	aucabove.trough.all	count.conc	count.conc.measured	totdose	volpk	ae	clr.last	clr.int.inf.pred	clr.int.inf.obs	clr.int.all	clr.int.last	clr.all	clr.inf.obs	clr.inf.pred	fe	ertlst	ermax	ertmax	erint	erlst	ratio.cmax	ratio.auclast	ratio.aucint.last	ratio.aucint.all	sparse_auclast	sparse_auc_se	sparse_auc_df	sparse_aumclast	sparse_aumc_se	sparse_aumc_df	time.above	aucivlast	aucivlast_se	aucivlast_df	aucivall	aucivall_se	aucivall_df	aucivpbext.last	aucivpbext.all	aumcivlast	aumcivlast_se	aumcivlast_df	aumcivall	aumcivall_se	aumcivall_df	half.life	r.squared	adj.r.squared	lambda.z.corrxy	lambda.z	lambda.z.time.first	lambda.z.time.last	lambda.z.n.points	clast.pred	span.ratio	tobit.residual	adj.tobit.residual	lambda.z.n.points.blq	thalf.eff.last	thalf.eff.int.all	thalf.eff.int.last	thalf.eff.all	thalf.eff.iv.last	thalf.eff.ivint.all	thalf.eff.ivint.last	kel.last	kel.iv.last	kel.all	kel.int.all	kel.int.last	kel.ivint.all	kel.ivint.last	cl.iv.all	cl.iv.last	cl.sparse.last	f.last	f.all	f.int.last	f.int.all	mrt.sparse.last	mrt.iv.all	vz.all	vz.int.all	vz.int.last	vz.iv.all	vz.iv.last	vz.ivint.all	vz.ivint.last	vz.last	vss.iv.all	vss.sparse.last	cav.iv.last	cav.iv.all	aucinf.obs	aucinf.obs_se	aucinf.obs_df	aucinf.pred	aumcinf.obs	aumcinf.obs_se	aumcinf.obs_df	aumcinf.pred	aucint.inf.obs	aucint.inf.pred	aumcint.inf.obs	aumcint.inf.pred	aucivint.inf.obs	aucivint.inf.pred	aucivinf.obs	aucivinf.obs_se	aucivinf.obs_df	aucivinf.pred	aucivpbext.inf.obs	aucivpbext.inf.pred	aumcivint.inf.pred	aumcivint.inf.obs	aumcivinf.obs	aumcivinf.obs_se	aumcivinf.obs_df	aumcivinf.pred	thalf.eff.iv.all	aucpext.inf.obs	aucpext.inf.pred	kel.iv.all	kel.sparse.last	cl.inf.obs	cl.inf.pred	cl.int.inf.obs	cl.int.inf.pred	cl.iv.inf.obs	cl.iv.inf.pred	cl.ivint.inf.pred	cl.ivint.inf.obs	f.inf.obs	f.inf.pred	f.int.inf.obs	f.int.inf.pred	mrt.inf.obs	mrt.inf.pred	mrt.int.inf.obs	mrt.int.inf.pred	mrt.iv.inf.obs	mrt.iv.inf.pred	mrt.ivint.inf.pred	mrt.ivint.inf.obs	mrt.md.inf.obs	mrt.md.inf.pred	mrt.ivmd.inf.obs	mrt.ivmd.inf.pred	vz.inf.obs	vz.inf.pred	vz.int.inf.obs	vz.int.inf.pred	vz.iv.inf.obs	vz.iv.inf.pred	vz.ivint.inf.pred	vz.ivint.inf.obs	vz.sparse.last	vss.inf.obs	vss.inf.pred	vss.iv.inf.obs	vss.iv.inf.pred	vss.md.inf.obs	vss.md.inf.pred	vss.ivmd.inf.obs	vss.ivmd.inf.pred	vss.int.inf.obs	vss.int.inf.pred	vss.ivint.inf.pred	vss.ivint.inf.obs	cav.int.inf.obs	cav.int.inf.pred	cav.ivint.inf.obs	cav.ivint.inf.pred	ratio.aucinf.obs	ratio.aucinf.pred	thalf.eff.inf.obs	thalf.eff.inf.pred	thalf.eff.int.inf.pred	thalf.eff.int.inf.obs	thalf.eff.iv.inf.obs	thalf.eff.iv.inf.pred	thalf.eff.ivint.inf.pred	thalf.eff.ivint.inf.obs	kel.inf.obs	kel.inf.pred	kel.iv.inf.obs	kel.iv.inf.pred	kel.int.inf.obs	kel.int.inf.pred	kel.ivint.inf.pred	kel.ivint.inf.obs	auclast.dn	aucall.dn	aucinf.obs.dn	aucinf.pred.dn	aumclast.dn	aumcall.dn	aumcinf.obs.dn	aumcinf.pred.dn	cmax.dn	cmin.dn	clast.obs.dn	clast.pred.dn	cav.last.dn	ctrough.dn	adj_tobit_residual	aucivpbextall	aucivpbextinf.obs	aucivpbextinf.pred	aucivpbextint.all	aucivpbextint.last	aucivpbextlast	aucpext.obs	aucpext.pred	cav	cav.dn	cl.iv.obs	cl.iv.pred	cl.obs	cl.pred	clr.obs	clr.pred	count_conc	count_conc_measured	f.int.obs	f.int.pred	f.obs	f.pred	kel.iv.obs	kel.iv.pred	kel.obs	kel.pred	lambda.z.n.points_blq	mrt.iv.obs	mrt.iv.pred	mrt.ivmd.obs	mrt.ivmd.pred	mrt.md.obs	mrt.md.pred	mrt.obs	mrt.pred	thalf.eff.iv.obs	thalf.eff.iv.pred	thalf.eff.obs	thalf.eff.pred	time_above	tobit_residual	vss.iv.obs	vss.iv.pred	vss.ivmd.obs	vss.ivmd.pred	vss.md.obs	vss.md.pred	vss.obs	vss.pred	vz.iv.obs	vz.iv.pred	vz.obs	vz.pred	Subject	impute
Inf	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	1	start_predose_conc0
Inf	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	2	start_predose_conc0
Inf	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	3	start_predose_conc0
Inf	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	4	start_predose_conc0
Inf	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	5	start_predose_conc0
Inf	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	6	start_predose_conc0
Inf	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	7	start_predose_conc0
Inf	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	8	start_predose_conc0
Inf	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	9	start_predose_conc0
Inf	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	10	start_predose_conc0
Inf	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	11	start_predose_conc0
Inf	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	12	start_predose_conc0

Intervals for calculation can also be specified manually. Manual specification requires at least columns for start time, end time, and the parameters requested. The manual specification can also include any grouping factors from the concentration data set. Column order of the intervals is not important. When intervals are manually specified, they are expanded to the full interval set when added to a PKNCAdata object (in other words, a column is created for each parameter). Also, PKNCA automatically calculates parameters required for the NCA, so while lambda.z is required for calculating AUC_{0- $\infty$}, you do not have to specify it in the parameters requested.

intervals_manual <- data.frame(start=0,
                               end=Inf,
                               cmax=TRUE,
                               tmax=TRUE,
                               aucinf.obs=TRUE,
                               auclast=TRUE)
data_obj_manual <- PKNCAdata(conc_obj, dose_obj,
                             intervals=intervals_manual)
knitr::kable(data_obj_manual$intervals)

start	end	auclast	auclast_se	auclast_df	aucall	aucall_se	aucall_df	aumclast	aumclast_se	aumclast_df	aumcall	aumcall_se	aumcall_df	aucint.last	aucint.all	aumcint.last	aumcint.all	aucivint.last	aucivint.all	aucivpbext.int.last	aucivpbext.int.all	aumcivint.last	aumcivint.all	c0	cmax	cmin	tmax	tmin	tlast	tfirst	clast.obs	cl.last	cl.all	cl.int.all	cl.int.last	cl.ivint.all	cl.ivint.last	mrt.last	mrt.all	mrt.int.all	mrt.int.last	mrt.iv.last	mrt.ivint.all	mrt.ivint.last	vss.last	vss.iv.last	vss.all	vss.int.all	vss.int.last	vss.ivint.all	vss.ivint.last	cav.last	cav.int.last	cav.int.all	cav.all	cav.ivint.last	cav.ivint.all	ctrough	cstart	ptr	tlag	deg.fluc	swing	ceoi	aucabove.predose.all	aucabove.trough.all	count.conc	count.conc.measured	totdose	volpk	ae	clr.last	clr.int.inf.pred	clr.int.inf.obs	clr.int.all	clr.int.last	clr.all	clr.inf.obs	clr.inf.pred	fe	ertlst	ermax	ertmax	erint	erlst	ratio.cmax	ratio.auclast	ratio.aucint.last	ratio.aucint.all	sparse_auclast	sparse_auc_se	sparse_auc_df	sparse_aumclast	sparse_aumc_se	sparse_aumc_df	time.above	aucivlast	aucivlast_se	aucivlast_df	aucivall	aucivall_se	aucivall_df	aucivpbext.last	aucivpbext.all	aumcivlast	aumcivlast_se	aumcivlast_df	aumcivall	aumcivall_se	aumcivall_df	half.life	r.squared	adj.r.squared	lambda.z.corrxy	lambda.z	lambda.z.time.first	lambda.z.time.last	lambda.z.n.points	clast.pred	span.ratio	tobit.residual	adj.tobit.residual	lambda.z.n.points.blq	thalf.eff.last	thalf.eff.int.all	thalf.eff.int.last	thalf.eff.all	thalf.eff.iv.last	thalf.eff.ivint.all	thalf.eff.ivint.last	kel.last	kel.iv.last	kel.all	kel.int.all	kel.int.last	kel.ivint.all	kel.ivint.last	cl.iv.all	cl.iv.last	cl.sparse.last	f.last	f.all	f.int.last	f.int.all	mrt.sparse.last	mrt.iv.all	vz.all	vz.int.all	vz.int.last	vz.iv.all	vz.iv.last	vz.ivint.all	vz.ivint.last	vz.last	vss.iv.all	vss.sparse.last	cav.iv.last	cav.iv.all	aucinf.obs	aucinf.obs_se	aucinf.obs_df	aucinf.pred	aumcinf.obs	aumcinf.obs_se	aumcinf.obs_df	aumcinf.pred	aucint.inf.obs	aucint.inf.pred	aumcint.inf.obs	aumcint.inf.pred	aucivint.inf.obs	aucivint.inf.pred	aucivinf.obs	aucivinf.obs_se	aucivinf.obs_df	aucivinf.pred	aucivpbext.inf.obs	aucivpbext.inf.pred	aumcivint.inf.pred	aumcivint.inf.obs	aumcivinf.obs	aumcivinf.obs_se	aumcivinf.obs_df	aumcivinf.pred	thalf.eff.iv.all	aucpext.inf.obs	aucpext.inf.pred	kel.iv.all	kel.sparse.last	cl.inf.obs	cl.inf.pred	cl.int.inf.obs	cl.int.inf.pred	cl.iv.inf.obs	cl.iv.inf.pred	cl.ivint.inf.pred	cl.ivint.inf.obs	f.inf.obs	f.inf.pred	f.int.inf.obs	f.int.inf.pred	mrt.inf.obs	mrt.inf.pred	mrt.int.inf.obs	mrt.int.inf.pred	mrt.iv.inf.obs	mrt.iv.inf.pred	mrt.ivint.inf.pred	mrt.ivint.inf.obs	mrt.md.inf.obs	mrt.md.inf.pred	mrt.ivmd.inf.obs	mrt.ivmd.inf.pred	vz.inf.obs	vz.inf.pred	vz.int.inf.obs	vz.int.inf.pred	vz.iv.inf.obs	vz.iv.inf.pred	vz.ivint.inf.pred	vz.ivint.inf.obs	vz.sparse.last	vss.inf.obs	vss.inf.pred	vss.iv.inf.obs	vss.iv.inf.pred	vss.md.inf.obs	vss.md.inf.pred	vss.ivmd.inf.obs	vss.ivmd.inf.pred	vss.int.inf.obs	vss.int.inf.pred	vss.ivint.inf.pred	vss.ivint.inf.obs	cav.int.inf.obs	cav.int.inf.pred	cav.ivint.inf.obs	cav.ivint.inf.pred	ratio.aucinf.obs	ratio.aucinf.pred	thalf.eff.inf.obs	thalf.eff.inf.pred	thalf.eff.int.inf.pred	thalf.eff.int.inf.obs	thalf.eff.iv.inf.obs	thalf.eff.iv.inf.pred	thalf.eff.ivint.inf.pred	thalf.eff.ivint.inf.obs	kel.inf.obs	kel.inf.pred	kel.iv.inf.obs	kel.iv.inf.pred	kel.int.inf.obs	kel.int.inf.pred	kel.ivint.inf.pred	kel.ivint.inf.obs	auclast.dn	aucall.dn	aucinf.obs.dn	aucinf.pred.dn	aumclast.dn	aumcall.dn	aumcinf.obs.dn	aumcinf.pred.dn	cmax.dn	cmin.dn	clast.obs.dn	clast.pred.dn	cav.last.dn	ctrough.dn	adj_tobit_residual	aucivpbextall	aucivpbextinf.obs	aucivpbextinf.pred	aucivpbextint.all	aucivpbextint.last	aucivpbextlast	aucpext.obs	aucpext.pred	cav	cav.dn	cl.iv.obs	cl.iv.pred	cl.obs	cl.pred	clr.obs	clr.pred	count_conc	count_conc_measured	f.int.obs	f.int.pred	f.obs	f.pred	kel.iv.obs	kel.iv.pred	kel.obs	kel.pred	lambda.z.n.points_blq	mrt.iv.obs	mrt.iv.pred	mrt.ivmd.obs	mrt.ivmd.pred	mrt.md.obs	mrt.md.pred	mrt.obs	mrt.pred	thalf.eff.iv.obs	thalf.eff.iv.pred	thalf.eff.obs	thalf.eff.pred	time_above	tobit_residual	vss.iv.obs	vss.iv.pred	vss.ivmd.obs	vss.ivmd.pred	vss.md.obs	vss.md.pred	vss.obs	vss.pred	vz.iv.obs	vz.iv.pred	vz.obs	vz.pred
0	Inf	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	TRUE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE	FALSE

Compute the parameters

Parameter calculation will automatically split the data by the grouping factor(s), subset by the interval, calculate all required parameters, record all options used for the calculations, and include data provenance to show that the calculation was performed as described. For all this, just call the pk.nca function with your PKNCAdata object.

results_obj_automatic <- pk.nca(data_obj_automatic)
knitr::kable(head(as.data.frame(results_obj_automatic)))

Subject	end	PPTESTCD	PPORRES	PPANMETH	exclude
1	Inf	auclast	147.2347	Imputation: start_predose_conc0. AUC: lin up/log down	NA
1	Inf	cmax	10.5000	Imputation: start_predose_conc0	NA
1	Inf	tmax	1.1200	Imputation: start_predose_conc0	NA
1	Inf	tlast	24.3700	Imputation: start_predose_conc0	NA
1	Inf	clast.obs	3.2800	Imputation: start_predose_conc0	NA
1	Inf	tlag	0.0000	Imputation: start_predose_conc0	NA

summary(results_obj_automatic)

start	end	N	auclast	cmax	tmax	tlag	count.conc	half.life	aucinf.obs	aucpext.inf.obs	cl.inf.obs
0	Inf	12	98.7 [22.5]	8.65 [17.0]	1.14 [0.630, 3.55]	0.000 [0.000, 0.000]	11.0 [11.0, 11.0]	8.18 [2.12]	115 [28.4]	13.8 [6.34]	0.0398 [29.4]

results_obj_manual <- pk.nca(data_obj_manual)
knitr::kable(head(as.data.frame(results_obj_manual)))

Subject	end	PPTESTCD	PPORRES	PPANMETH	exclude
6	Inf	auclast	71.6970150	AUC: lin up/log down	NA
6	Inf	cmax	6.4400000		NA
6	Inf	tmax	1.1500000		NA
6	Inf	tlast	23.8500000		NA
6	Inf	clast.obs	0.9200000		NA
6	Inf	lambda.z	0.0877957		NA

summary(results_obj_manual)

start	end	N	auclast	cmax	tmax	aucinf.obs
0	Inf	12	98.7 [22.5]	8.65 [17.0]	1.14 [0.630, 3.55]	115 [28.4]

Multiple Dose Example

Assessing multiple dose pharmacokinetics is conceptually the same as single-dose in PKNCA.

To assess multiple dose PK, the theophylline data will be extended from single to multiple doses using superposition (see the superposition vignette for more information).

conc_obj <- PKNCAconc(as.data.frame(datasets::Theoph), conc~Time|Subject)
conc_obj_multi <-
  PKNCAconc(
    superposition(conc_obj,
                  tau=168,
                  dose.times=seq(0, 144, by=24),
                  n.tau=1,
                  check.blq=FALSE),
    conc~time|Subject)
conc_obj_multi

## Formula for concentration:
##  conc ~ time | Subject
## Data are dense PK.
## With 12 subjects defined in the 'Subject' column.
## Nominal time column is not specified.
## 
## First 6 rows of concentration data:
##  Subject     conc time exclude
##        1  0.74000 0.00    <NA>
##        1  2.84000 0.25    <NA>
##        1  4.23875 0.37    <NA>
##        1  6.57000 0.57    <NA>
##        1 10.50000 1.12    <NA>
##        1  9.66000 2.02    <NA>

dose_obj_multi <- PKNCAdose(expand.grid(Subject=unique(as.data.frame(conc_obj_multi)$Subject),
                                      time=seq(0, 144, by=24)),
                          ~time|Subject)
dose_obj_multi

## Formula for dosing:
##  ~time | Subject
## Nominal time column is not specified.
## 
## First 6 rows of dosing data:
##  Subject time exclude         route duration
##        1    0    <NA> extravascular        0
##        2    0    <NA> extravascular        0
##        3    0    <NA> extravascular        0
##        4    0    <NA> extravascular        0
##        5    0    <NA> extravascular        0
##        6    0    <NA> extravascular        0

The superposition-simulated scenario is not especially realistic as it includes dense sampling on every day. With this scenario, the intervals automatically selected have an interval for every subject on every day.

data_obj <- PKNCAdata(conc_obj_multi, dose_obj_multi)
data_obj$intervals[,c("Subject", "start", "end")]

## # A tibble: 84 × 3
##    Subject start   end
##    <ord>   <dbl> <dbl>
##  1 1           0    24
##  2 1          24    48
##  3 1          48    72
##  4 1          72    96
##  5 1          96   120
##  6 1         120   144
##  7 1         144   168
##  8 2           0    24
##  9 2          24    48
## 10 2          48    72
## # ℹ 74 more rows

In a more realistic scenario, dense PK sampling occurs for every subject on the first and last days. To select those intervals manually, specify the intervals of interest in the intervals argument to the PKNCAdata function call. The intervals are automatically expanded not to calculate anything that was not requested.

intervals_manual <- data.frame(start=c(0, 144),
                               end=c(24, 168),
                               cmax=TRUE,
                               auclast=TRUE)
data_obj <- PKNCAdata(conc_obj_multi, dose_obj_multi,
                      intervals=intervals_manual)
data_obj$intervals

##   start end auclast auclast_se auclast_df aucall aucall_se aucall_df aumclast
## 1     0  24    TRUE      FALSE      FALSE  FALSE     FALSE     FALSE    FALSE
## 2   144 168    TRUE      FALSE      FALSE  FALSE     FALSE     FALSE    FALSE
##   aumclast_se aumclast_df aumcall aumcall_se aumcall_df aucint.last aucint.all
## 1       FALSE       FALSE   FALSE      FALSE      FALSE       FALSE      FALSE
## 2       FALSE       FALSE   FALSE      FALSE      FALSE       FALSE      FALSE
##   aumcint.last aumcint.all aucivint.last aucivint.all aucivpbext.int.last
## 1        FALSE       FALSE         FALSE        FALSE               FALSE
## 2        FALSE       FALSE         FALSE        FALSE               FALSE
##   aucivpbext.int.all aumcivint.last aumcivint.all    c0 cmax  cmin  tmax  tmin
## 1              FALSE          FALSE         FALSE FALSE TRUE FALSE FALSE FALSE
## 2              FALSE          FALSE         FALSE FALSE TRUE FALSE FALSE FALSE
##   tlast tfirst clast.obs cl.last cl.all cl.int.all cl.int.last cl.ivint.all
## 1 FALSE  FALSE     FALSE   FALSE  FALSE      FALSE       FALSE        FALSE
## 2 FALSE  FALSE     FALSE   FALSE  FALSE      FALSE       FALSE        FALSE
##   cl.ivint.last mrt.last mrt.all mrt.int.all mrt.int.last mrt.iv.last
## 1         FALSE    FALSE   FALSE       FALSE        FALSE       FALSE
## 2         FALSE    FALSE   FALSE       FALSE        FALSE       FALSE
##   mrt.ivint.all mrt.ivint.last vss.last vss.iv.last vss.all vss.int.all
## 1         FALSE          FALSE    FALSE       FALSE   FALSE       FALSE
## 2         FALSE          FALSE    FALSE       FALSE   FALSE       FALSE
##   vss.int.last vss.ivint.all vss.ivint.last cav.last cav.int.last cav.int.all
## 1        FALSE         FALSE          FALSE    FALSE        FALSE       FALSE
## 2        FALSE         FALSE          FALSE    FALSE        FALSE       FALSE
##   cav.all cav.ivint.last cav.ivint.all ctrough cstart   ptr  tlag deg.fluc
## 1   FALSE          FALSE         FALSE   FALSE  FALSE FALSE FALSE    FALSE
## 2   FALSE          FALSE         FALSE   FALSE  FALSE FALSE FALSE    FALSE
##   swing  ceoi aucabove.predose.all aucabove.trough.all count.conc
## 1 FALSE FALSE                FALSE               FALSE      FALSE
## 2 FALSE FALSE                FALSE               FALSE      FALSE
##   count.conc.measured totdose volpk    ae clr.last clr.int.inf.pred
## 1               FALSE   FALSE FALSE FALSE    FALSE            FALSE
## 2               FALSE   FALSE FALSE FALSE    FALSE            FALSE
##   clr.int.inf.obs clr.int.all clr.int.last clr.all clr.inf.obs clr.inf.pred
## 1           FALSE       FALSE        FALSE   FALSE       FALSE        FALSE
## 2           FALSE       FALSE        FALSE   FALSE       FALSE        FALSE
##      fe ertlst ermax ertmax erint erlst ratio.cmax ratio.auclast
## 1 FALSE  FALSE FALSE  FALSE FALSE FALSE      FALSE         FALSE
## 2 FALSE  FALSE FALSE  FALSE FALSE FALSE      FALSE         FALSE
##   ratio.aucint.last ratio.aucint.all sparse_auclast sparse_auc_se sparse_auc_df
## 1             FALSE            FALSE          FALSE         FALSE         FALSE
## 2             FALSE            FALSE          FALSE         FALSE         FALSE
##   sparse_aumclast sparse_aumc_se sparse_aumc_df time.above aucivlast
## 1           FALSE          FALSE          FALSE      FALSE     FALSE
## 2           FALSE          FALSE          FALSE      FALSE     FALSE
##   aucivlast_se aucivlast_df aucivall aucivall_se aucivall_df aucivpbext.last
## 1        FALSE        FALSE    FALSE       FALSE       FALSE           FALSE
## 2        FALSE        FALSE    FALSE       FALSE       FALSE           FALSE
##   aucivpbext.all aumcivlast aumcivlast_se aumcivlast_df aumcivall aumcivall_se
## 1          FALSE      FALSE         FALSE         FALSE     FALSE        FALSE
## 2          FALSE      FALSE         FALSE         FALSE     FALSE        FALSE
##   aumcivall_df half.life r.squared adj.r.squared lambda.z.corrxy lambda.z
## 1        FALSE     FALSE     FALSE         FALSE           FALSE    FALSE
## 2        FALSE     FALSE     FALSE         FALSE           FALSE    FALSE
##   lambda.z.time.first lambda.z.time.last lambda.z.n.points clast.pred
## 1               FALSE              FALSE             FALSE      FALSE
## 2               FALSE              FALSE             FALSE      FALSE
##   span.ratio tobit.residual adj.tobit.residual lambda.z.n.points.blq
## 1      FALSE          FALSE              FALSE                 FALSE
## 2      FALSE          FALSE              FALSE                 FALSE
##   thalf.eff.last thalf.eff.int.all thalf.eff.int.last thalf.eff.all
## 1          FALSE             FALSE              FALSE         FALSE
## 2          FALSE             FALSE              FALSE         FALSE
##   thalf.eff.iv.last thalf.eff.ivint.all thalf.eff.ivint.last kel.last
## 1             FALSE               FALSE                FALSE    FALSE
## 2             FALSE               FALSE                FALSE    FALSE
##   kel.iv.last kel.all kel.int.all kel.int.last kel.ivint.all kel.ivint.last
## 1       FALSE   FALSE       FALSE        FALSE         FALSE          FALSE
## 2       FALSE   FALSE       FALSE        FALSE         FALSE          FALSE
##   cl.iv.all cl.iv.last cl.sparse.last f.last f.all f.int.last f.int.all
## 1     FALSE      FALSE          FALSE  FALSE FALSE      FALSE     FALSE
## 2     FALSE      FALSE          FALSE  FALSE FALSE      FALSE     FALSE
##   mrt.sparse.last mrt.iv.all vz.all vz.int.all vz.int.last vz.iv.all vz.iv.last
## 1           FALSE      FALSE  FALSE      FALSE       FALSE     FALSE      FALSE
## 2           FALSE      FALSE  FALSE      FALSE       FALSE     FALSE      FALSE
##   vz.ivint.all vz.ivint.last vz.last vss.iv.all vss.sparse.last cav.iv.last
## 1        FALSE         FALSE   FALSE      FALSE           FALSE       FALSE
## 2        FALSE         FALSE   FALSE      FALSE           FALSE       FALSE
##   cav.iv.all aucinf.obs aucinf.obs_se aucinf.obs_df aucinf.pred aumcinf.obs
## 1      FALSE      FALSE         FALSE         FALSE       FALSE       FALSE
## 2      FALSE      FALSE         FALSE         FALSE       FALSE       FALSE
##   aumcinf.obs_se aumcinf.obs_df aumcinf.pred aucint.inf.obs aucint.inf.pred
## 1          FALSE          FALSE        FALSE          FALSE           FALSE
## 2          FALSE          FALSE        FALSE          FALSE           FALSE
##   aumcint.inf.obs aumcint.inf.pred aucivint.inf.obs aucivint.inf.pred
## 1           FALSE            FALSE            FALSE             FALSE
## 2           FALSE            FALSE            FALSE             FALSE
##   aucivinf.obs aucivinf.obs_se aucivinf.obs_df aucivinf.pred aucivpbext.inf.obs
## 1        FALSE           FALSE           FALSE         FALSE              FALSE
## 2        FALSE           FALSE           FALSE         FALSE              FALSE
##   aucivpbext.inf.pred aumcivint.inf.pred aumcivint.inf.obs aumcivinf.obs
## 1               FALSE              FALSE             FALSE         FALSE
## 2               FALSE              FALSE             FALSE         FALSE
##   aumcivinf.obs_se aumcivinf.obs_df aumcivinf.pred thalf.eff.iv.all
## 1            FALSE            FALSE          FALSE            FALSE
## 2            FALSE            FALSE          FALSE            FALSE
##   aucpext.inf.obs aucpext.inf.pred kel.iv.all kel.sparse.last cl.inf.obs
## 1           FALSE            FALSE      FALSE           FALSE      FALSE
## 2           FALSE            FALSE      FALSE           FALSE      FALSE
##   cl.inf.pred cl.int.inf.obs cl.int.inf.pred cl.iv.inf.obs cl.iv.inf.pred
## 1       FALSE          FALSE           FALSE         FALSE          FALSE
## 2       FALSE          FALSE           FALSE         FALSE          FALSE
##   cl.ivint.inf.pred cl.ivint.inf.obs f.inf.obs f.inf.pred f.int.inf.obs
## 1             FALSE            FALSE     FALSE      FALSE         FALSE
## 2             FALSE            FALSE     FALSE      FALSE         FALSE
##   f.int.inf.pred mrt.inf.obs mrt.inf.pred mrt.int.inf.obs mrt.int.inf.pred
## 1          FALSE       FALSE        FALSE           FALSE            FALSE
## 2          FALSE       FALSE        FALSE           FALSE            FALSE
##   mrt.iv.inf.obs mrt.iv.inf.pred mrt.ivint.inf.pred mrt.ivint.inf.obs
## 1          FALSE           FALSE              FALSE             FALSE
## 2          FALSE           FALSE              FALSE             FALSE
##   mrt.md.inf.obs mrt.md.inf.pred mrt.ivmd.inf.obs mrt.ivmd.inf.pred vz.inf.obs
## 1          FALSE           FALSE            FALSE             FALSE      FALSE
## 2          FALSE           FALSE            FALSE             FALSE      FALSE
##   vz.inf.pred vz.int.inf.obs vz.int.inf.pred vz.iv.inf.obs vz.iv.inf.pred
## 1       FALSE          FALSE           FALSE         FALSE          FALSE
## 2       FALSE          FALSE           FALSE         FALSE          FALSE
##   vz.ivint.inf.pred vz.ivint.inf.obs vz.sparse.last vss.inf.obs vss.inf.pred
## 1             FALSE            FALSE          FALSE       FALSE        FALSE
## 2             FALSE            FALSE          FALSE       FALSE        FALSE
##   vss.iv.inf.obs vss.iv.inf.pred vss.md.inf.obs vss.md.inf.pred
## 1          FALSE           FALSE          FALSE           FALSE
## 2          FALSE           FALSE          FALSE           FALSE
##   vss.ivmd.inf.obs vss.ivmd.inf.pred vss.int.inf.obs vss.int.inf.pred
## 1            FALSE             FALSE           FALSE            FALSE
## 2            FALSE             FALSE           FALSE            FALSE
##   vss.ivint.inf.pred vss.ivint.inf.obs cav.int.inf.obs cav.int.inf.pred
## 1              FALSE             FALSE           FALSE            FALSE
## 2              FALSE             FALSE           FALSE            FALSE
##   cav.ivint.inf.obs cav.ivint.inf.pred ratio.aucinf.obs ratio.aucinf.pred
## 1             FALSE              FALSE            FALSE             FALSE
## 2             FALSE              FALSE            FALSE             FALSE
##   thalf.eff.inf.obs thalf.eff.inf.pred thalf.eff.int.inf.pred
## 1             FALSE              FALSE                  FALSE
## 2             FALSE              FALSE                  FALSE
##   thalf.eff.int.inf.obs thalf.eff.iv.inf.obs thalf.eff.iv.inf.pred
## 1                 FALSE                FALSE                 FALSE
## 2                 FALSE                FALSE                 FALSE
##   thalf.eff.ivint.inf.pred thalf.eff.ivint.inf.obs kel.inf.obs kel.inf.pred
## 1                    FALSE                   FALSE       FALSE        FALSE
## 2                    FALSE                   FALSE       FALSE        FALSE
##   kel.iv.inf.obs kel.iv.inf.pred kel.int.inf.obs kel.int.inf.pred
## 1          FALSE           FALSE           FALSE            FALSE
## 2          FALSE           FALSE           FALSE            FALSE
##   kel.ivint.inf.pred kel.ivint.inf.obs auclast.dn aucall.dn aucinf.obs.dn
## 1              FALSE             FALSE      FALSE     FALSE         FALSE
## 2              FALSE             FALSE      FALSE     FALSE         FALSE
##   aucinf.pred.dn aumclast.dn aumcall.dn aumcinf.obs.dn aumcinf.pred.dn cmax.dn
## 1          FALSE       FALSE      FALSE          FALSE           FALSE   FALSE
## 2          FALSE       FALSE      FALSE          FALSE           FALSE   FALSE
##   cmin.dn clast.obs.dn clast.pred.dn cav.last.dn ctrough.dn adj_tobit_residual
## 1   FALSE        FALSE         FALSE       FALSE      FALSE              FALSE
## 2   FALSE        FALSE         FALSE       FALSE      FALSE              FALSE
##   aucivpbextall aucivpbextinf.obs aucivpbextinf.pred aucivpbextint.all
## 1         FALSE             FALSE              FALSE             FALSE
## 2         FALSE             FALSE              FALSE             FALSE
##   aucivpbextint.last aucivpbextlast aucpext.obs aucpext.pred   cav cav.dn
## 1              FALSE          FALSE       FALSE        FALSE FALSE  FALSE
## 2              FALSE          FALSE       FALSE        FALSE FALSE  FALSE
##   cl.iv.obs cl.iv.pred cl.obs cl.pred clr.obs clr.pred count_conc
## 1     FALSE      FALSE  FALSE   FALSE   FALSE    FALSE      FALSE
## 2     FALSE      FALSE  FALSE   FALSE   FALSE    FALSE      FALSE
##   count_conc_measured f.int.obs f.int.pred f.obs f.pred kel.iv.obs kel.iv.pred
## 1               FALSE     FALSE      FALSE FALSE  FALSE      FALSE       FALSE
## 2               FALSE     FALSE      FALSE FALSE  FALSE      FALSE       FALSE
##   kel.obs kel.pred lambda.z.n.points_blq mrt.iv.obs mrt.iv.pred mrt.ivmd.obs
## 1   FALSE    FALSE                 FALSE      FALSE       FALSE        FALSE
## 2   FALSE    FALSE                 FALSE      FALSE       FALSE        FALSE
##   mrt.ivmd.pred mrt.md.obs mrt.md.pred mrt.obs mrt.pred thalf.eff.iv.obs
## 1         FALSE      FALSE       FALSE   FALSE    FALSE            FALSE
## 2         FALSE      FALSE       FALSE   FALSE    FALSE            FALSE
##   thalf.eff.iv.pred thalf.eff.obs thalf.eff.pred time_above tobit_residual
## 1             FALSE         FALSE          FALSE      FALSE          FALSE
## 2             FALSE         FALSE          FALSE      FALSE          FALSE
##   vss.iv.obs vss.iv.pred vss.ivmd.obs vss.ivmd.pred vss.md.obs vss.md.pred
## 1      FALSE       FALSE        FALSE         FALSE      FALSE       FALSE
## 2      FALSE       FALSE        FALSE         FALSE      FALSE       FALSE
##   vss.obs vss.pred vz.iv.obs vz.iv.pred vz.obs vz.pred
## 1   FALSE    FALSE     FALSE      FALSE  FALSE   FALSE
## 2   FALSE    FALSE     FALSE      FALSE  FALSE   FALSE

After the data is ready, the calculations and summary can progress.

results_obj <- pk.nca(data_obj)
print(results_obj)

## $result
## # A tibble: 48 × 7
##    Subject start   end PPTESTCD PPORRES PPANMETH               exclude
##    <ord>   <dbl> <dbl> <chr>      <dbl> <chr>                  <chr>  
##  1 6           0    24 auclast    71.8  "AUC: lin up/log down" NA     
##  2 6           0    24 cmax        6.44 ""                     NA     
##  3 6         144   168 auclast    82.2  "AUC: lin up/log down" NA     
##  4 6         144   168 cmax        7.37 ""                     NA     
##  5 7           0    24 auclast    89.0  "AUC: lin up/log down" NA     
##  6 7           0    24 cmax        7.09 ""                     NA     
##  7 7         144   168 auclast   101.   "AUC: lin up/log down" NA     
##  8 7         144   168 cmax        8.07 ""                     NA     
##  9 8           0    24 auclast    86.7  "AUC: lin up/log down" NA     
## 10 8           0    24 cmax        7.56 ""                     NA     
## # ℹ 38 more rows
## 
## $data
## Formula for concentration:
##  conc ~ time | Subject
## Data are dense PK.
## With 12 subjects defined in the 'Subject' column.
## Nominal time column is not specified.
## 
## First 6 rows of concentration data:
##  Subject     conc time exclude
##        1  0.74000 0.00    <NA>
##        1  2.84000 0.25    <NA>
##        1  4.23875 0.37    <NA>
##        1  6.57000 0.57    <NA>
##        1 10.50000 1.12    <NA>
##        1  9.66000 2.02    <NA>
## Formula for dosing:
##  ~time | Subject
## Nominal time column is not specified.
## 
## First 6 rows of dosing data:
##  Subject time exclude         route duration
##        1    0    <NA> extravascular        0
##        2    0    <NA> extravascular        0
##        3    0    <NA> extravascular        0
##        4    0    <NA> extravascular        0
##        5    0    <NA> extravascular        0
##        6    0    <NA> extravascular        0
## 
## With 2 rows of interval specifications.
## Options changed from default are:
## $adj.r.squared.factor
## [1] 1e-04
## 
## $r.squared.factor
## [1] NA
## 
## $max.missing
## [1] 0.5
## 
## $auc.method
## [1] "lin up/log down"
## 
## $conc.na
## [1] "drop"
## 
## $conc.blq
## $conc.blq$first
## [1] "keep"
## 
## $conc.blq$middle
## [1] "drop"
## 
## $conc.blq$last
## [1] "keep"
## 
## 
## $debug
## NULL
## 
## $first.tmax
## [1] TRUE
## 
## $first.tmin
## [1] TRUE
## 
## $allow.tmax.in.half.life
## [1] FALSE
## 
## $keep_interval_cols
## NULL
## 
## $min.hl.points
## [1] 3
## 
## $max.hl.points
## [1] Inf
## 
## $min.hl.start.time
## [1] 0
## 
## $min.span.ratio
## [1] 2
## 
## $max.aucinf.pext
## [1] 20
## 
## $min.hl.r.squared
## [1] 0.9
## 
## $progress
## [1] TRUE
## 
## $tau.choices
## [1] NA
## 
## $auto.interval.method
## [1] "builder"
## 
## $auto.interval.tolerance
## [1] 0.05
## 
## $single.dose.aucs
##   start end auclast auclast_se auclast_df aucall aucall_se aucall_df aumclast
## 1     0  24    TRUE      FALSE      FALSE  FALSE     FALSE     FALSE    FALSE
## 2     0 Inf   FALSE      FALSE      FALSE  FALSE     FALSE     FALSE    FALSE
##   aumclast_se aumclast_df aumcall aumcall_se aumcall_df aucint.last aucint.all
## 1       FALSE       FALSE   FALSE      FALSE      FALSE       FALSE      FALSE
## 2       FALSE       FALSE   FALSE      FALSE      FALSE       FALSE      FALSE
##   aumcint.last aumcint.all aucivint.last aucivint.all aucivpbext.int.last
## 1        FALSE       FALSE         FALSE        FALSE               FALSE
## 2        FALSE       FALSE         FALSE        FALSE               FALSE
##   aucivpbext.int.all aumcivint.last aumcivint.all    c0  cmax  cmin  tmax  tmin
## 1              FALSE          FALSE         FALSE FALSE FALSE FALSE FALSE FALSE
## 2              FALSE          FALSE         FALSE FALSE  TRUE FALSE  TRUE FALSE
##   tlast tfirst clast.obs cl.last cl.all cl.int.all cl.int.last cl.ivint.all
## 1 FALSE  FALSE     FALSE   FALSE  FALSE      FALSE       FALSE        FALSE
## 2 FALSE  FALSE     FALSE   FALSE  FALSE      FALSE       FALSE        FALSE
##   cl.ivint.last mrt.last mrt.all mrt.int.all mrt.int.last mrt.iv.last
## 1         FALSE    FALSE   FALSE       FALSE        FALSE       FALSE
## 2         FALSE    FALSE   FALSE       FALSE        FALSE       FALSE
##   mrt.ivint.all mrt.ivint.last vss.last vss.iv.last vss.all vss.int.all
## 1         FALSE          FALSE    FALSE       FALSE   FALSE       FALSE
## 2         FALSE          FALSE    FALSE       FALSE   FALSE       FALSE
##   vss.int.last vss.ivint.all vss.ivint.last cav.last cav.int.last cav.int.all
## 1        FALSE         FALSE          FALSE    FALSE        FALSE       FALSE
## 2        FALSE         FALSE          FALSE    FALSE        FALSE       FALSE
##   cav.all cav.ivint.last cav.ivint.all ctrough cstart   ptr  tlag deg.fluc
## 1   FALSE          FALSE         FALSE   FALSE  FALSE FALSE FALSE    FALSE
## 2   FALSE          FALSE         FALSE   FALSE  FALSE FALSE FALSE    FALSE
##   swing  ceoi aucabove.predose.all aucabove.trough.all count.conc
## 1 FALSE FALSE                FALSE               FALSE      FALSE
## 2 FALSE FALSE                FALSE               FALSE      FALSE
##   count.conc.measured totdose volpk    ae clr.last clr.int.inf.pred
## 1               FALSE   FALSE FALSE FALSE    FALSE            FALSE
## 2               FALSE   FALSE FALSE FALSE    FALSE            FALSE
##   clr.int.inf.obs clr.int.all clr.int.last clr.all clr.inf.obs clr.inf.pred
## 1           FALSE       FALSE        FALSE   FALSE       FALSE        FALSE
## 2           FALSE       FALSE        FALSE   FALSE       FALSE        FALSE
##      fe ertlst ermax ertmax erint erlst ratio.cmax ratio.auclast
## 1 FALSE  FALSE FALSE  FALSE FALSE FALSE      FALSE         FALSE
## 2 FALSE  FALSE FALSE  FALSE FALSE FALSE      FALSE         FALSE
##   ratio.aucint.last ratio.aucint.all sparse_auclast sparse_auc_se sparse_auc_df
## 1             FALSE            FALSE          FALSE         FALSE         FALSE
## 2             FALSE            FALSE          FALSE         FALSE         FALSE
##   sparse_aumclast sparse_aumc_se sparse_aumc_df time.above aucivlast
## 1           FALSE          FALSE          FALSE      FALSE     FALSE
## 2           FALSE          FALSE          FALSE      FALSE     FALSE
##   aucivlast_se aucivlast_df aucivall aucivall_se aucivall_df aucivpbext.last
## 1        FALSE        FALSE    FALSE       FALSE       FALSE           FALSE
## 2        FALSE        FALSE    FALSE       FALSE       FALSE           FALSE
##   aucivpbext.all aumcivlast aumcivlast_se aumcivlast_df aumcivall aumcivall_se
## 1          FALSE      FALSE         FALSE         FALSE     FALSE        FALSE
## 2          FALSE      FALSE         FALSE         FALSE     FALSE        FALSE
##   aumcivall_df half.life r.squared adj.r.squared lambda.z.corrxy lambda.z
## 1        FALSE     FALSE     FALSE         FALSE           FALSE    FALSE
## 2        FALSE      TRUE     FALSE         FALSE           FALSE    FALSE
##   lambda.z.time.first lambda.z.time.last lambda.z.n.points clast.pred
## 1               FALSE              FALSE             FALSE      FALSE
## 2               FALSE              FALSE             FALSE      FALSE
##   span.ratio tobit.residual adj.tobit.residual lambda.z.n.points.blq
## 1      FALSE          FALSE              FALSE                 FALSE
## 2      FALSE          FALSE              FALSE                 FALSE
##   thalf.eff.last thalf.eff.int.all thalf.eff.int.last thalf.eff.all
## 1          FALSE             FALSE              FALSE         FALSE
## 2          FALSE             FALSE              FALSE         FALSE
##   thalf.eff.iv.last thalf.eff.ivint.all thalf.eff.ivint.last kel.last
## 1             FALSE               FALSE                FALSE    FALSE
## 2             FALSE               FALSE                FALSE    FALSE
##   kel.iv.last kel.all kel.int.all kel.int.last kel.ivint.all kel.ivint.last
## 1       FALSE   FALSE       FALSE        FALSE         FALSE          FALSE
## 2       FALSE   FALSE       FALSE        FALSE         FALSE          FALSE
##   cl.iv.all cl.iv.last cl.sparse.last f.last f.all f.int.last f.int.all
## 1     FALSE      FALSE          FALSE  FALSE FALSE      FALSE     FALSE
## 2     FALSE      FALSE          FALSE  FALSE FALSE      FALSE     FALSE
##   mrt.sparse.last mrt.iv.all vz.all vz.int.all vz.int.last vz.iv.all vz.iv.last
## 1           FALSE      FALSE  FALSE      FALSE       FALSE     FALSE      FALSE
## 2           FALSE      FALSE  FALSE      FALSE       FALSE     FALSE      FALSE
##   vz.ivint.all vz.ivint.last vz.last vss.iv.all vss.sparse.last cav.iv.last
## 1        FALSE         FALSE   FALSE      FALSE           FALSE       FALSE
## 2        FALSE         FALSE   FALSE      FALSE           FALSE       FALSE
##   cav.iv.all aucinf.obs aucinf.obs_se aucinf.obs_df aucinf.pred aumcinf.obs
## 1      FALSE      FALSE         FALSE         FALSE       FALSE       FALSE
## 2      FALSE       TRUE         FALSE         FALSE       FALSE       FALSE
##   aumcinf.obs_se aumcinf.obs_df aumcinf.pred aucint.inf.obs aucint.inf.pred
## 1          FALSE          FALSE        FALSE          FALSE           FALSE
## 2          FALSE          FALSE        FALSE          FALSE           FALSE
##   aumcint.inf.obs aumcint.inf.pred aucivint.inf.obs aucivint.inf.pred
## 1           FALSE            FALSE            FALSE             FALSE
## 2           FALSE            FALSE            FALSE             FALSE
##   aucivinf.obs aucivinf.obs_se aucivinf.obs_df aucivinf.pred aucivpbext.inf.obs
## 1        FALSE           FALSE           FALSE         FALSE              FALSE
## 2        FALSE           FALSE           FALSE         FALSE              FALSE
##   aucivpbext.inf.pred aumcivint.inf.pred aumcivint.inf.obs aumcivinf.obs
## 1               FALSE              FALSE             FALSE         FALSE
## 2               FALSE              FALSE             FALSE         FALSE
##   aumcivinf.obs_se aumcivinf.obs_df aumcivinf.pred thalf.eff.iv.all
## 1            FALSE            FALSE          FALSE            FALSE
## 2            FALSE            FALSE          FALSE            FALSE
##   aucpext.inf.obs aucpext.inf.pred kel.iv.all kel.sparse.last cl.inf.obs
## 1           FALSE            FALSE      FALSE           FALSE      FALSE
## 2           FALSE            FALSE      FALSE           FALSE      FALSE
##   cl.inf.pred cl.int.inf.obs cl.int.inf.pred cl.iv.inf.obs cl.iv.inf.pred
## 1       FALSE          FALSE           FALSE         FALSE          FALSE
## 2       FALSE          FALSE           FALSE         FALSE          FALSE
##   cl.ivint.inf.pred cl.ivint.inf.obs f.inf.obs f.inf.pred f.int.inf.obs
## 1             FALSE            FALSE     FALSE      FALSE         FALSE
## 2             FALSE            FALSE     FALSE      FALSE         FALSE
##   f.int.inf.pred mrt.inf.obs mrt.inf.pred mrt.int.inf.obs mrt.int.inf.pred
## 1          FALSE       FALSE        FALSE           FALSE            FALSE
## 2          FALSE       FALSE        FALSE           FALSE            FALSE
##   mrt.iv.inf.obs mrt.iv.inf.pred mrt.ivint.inf.pred mrt.ivint.inf.obs
## 1          FALSE           FALSE              FALSE             FALSE
## 2          FALSE           FALSE              FALSE             FALSE
##   mrt.md.inf.obs mrt.md.inf.pred mrt.ivmd.inf.obs mrt.ivmd.inf.pred vz.inf.obs
## 1          FALSE           FALSE            FALSE             FALSE      FALSE
## 2          FALSE           FALSE            FALSE             FALSE      FALSE
##   vz.inf.pred vz.int.inf.obs vz.int.inf.pred vz.iv.inf.obs vz.iv.inf.pred
## 1       FALSE          FALSE           FALSE         FALSE          FALSE
## 2       FALSE          FALSE           FALSE         FALSE          FALSE
##   vz.ivint.inf.pred vz.ivint.inf.obs vz.sparse.last vss.inf.obs vss.inf.pred
## 1             FALSE            FALSE          FALSE       FALSE        FALSE
## 2             FALSE            FALSE          FALSE       FALSE        FALSE
##   vss.iv.inf.obs vss.iv.inf.pred vss.md.inf.obs vss.md.inf.pred
## 1          FALSE           FALSE          FALSE           FALSE
## 2          FALSE           FALSE          FALSE           FALSE
##   vss.ivmd.inf.obs vss.ivmd.inf.pred vss.int.inf.obs vss.int.inf.pred
## 1            FALSE             FALSE           FALSE            FALSE
## 2            FALSE             FALSE           FALSE            FALSE
##   vss.ivint.inf.pred vss.ivint.inf.obs cav.int.inf.obs cav.int.inf.pred
## 1              FALSE             FALSE           FALSE            FALSE
## 2              FALSE             FALSE           FALSE            FALSE
##   cav.ivint.inf.obs cav.ivint.inf.pred ratio.aucinf.obs ratio.aucinf.pred
## 1             FALSE              FALSE            FALSE             FALSE
## 2             FALSE              FALSE            FALSE             FALSE
##   thalf.eff.inf.obs thalf.eff.inf.pred thalf.eff.int.inf.pred
## 1             FALSE              FALSE                  FALSE
## 2             FALSE              FALSE                  FALSE
##   thalf.eff.int.inf.obs thalf.eff.iv.inf.obs thalf.eff.iv.inf.pred
## 1                 FALSE                FALSE                 FALSE
## 2                 FALSE                FALSE                 FALSE
##   thalf.eff.ivint.inf.pred thalf.eff.ivint.inf.obs kel.inf.obs kel.inf.pred
## 1                    FALSE                   FALSE       FALSE        FALSE
## 2                    FALSE                   FALSE       FALSE        FALSE
##   kel.iv.inf.obs kel.iv.inf.pred kel.int.inf.obs kel.int.inf.pred
## 1          FALSE           FALSE           FALSE            FALSE
## 2          FALSE           FALSE           FALSE            FALSE
##   kel.ivint.inf.pred kel.ivint.inf.obs auclast.dn aucall.dn aucinf.obs.dn
## 1              FALSE             FALSE      FALSE     FALSE         FALSE
## 2              FALSE             FALSE      FALSE     FALSE         FALSE
##   aucinf.pred.dn aumclast.dn aumcall.dn aumcinf.obs.dn aumcinf.pred.dn cmax.dn
## 1          FALSE       FALSE      FALSE          FALSE           FALSE   FALSE
## 2          FALSE       FALSE      FALSE          FALSE           FALSE   FALSE
##   cmin.dn clast.obs.dn clast.pred.dn cav.last.dn ctrough.dn adj_tobit_residual
## 1   FALSE        FALSE         FALSE       FALSE      FALSE              FALSE
## 2   FALSE        FALSE         FALSE       FALSE      FALSE              FALSE
##   aucivpbextall aucivpbextinf.obs aucivpbextinf.pred aucivpbextint.all
## 1         FALSE             FALSE              FALSE             FALSE
## 2         FALSE             FALSE              FALSE             FALSE
##   aucivpbextint.last aucivpbextlast aucpext.obs aucpext.pred   cav cav.dn
## 1              FALSE          FALSE       FALSE        FALSE FALSE  FALSE
## 2              FALSE          FALSE       FALSE        FALSE FALSE  FALSE
##   cl.iv.obs cl.iv.pred cl.obs cl.pred clr.obs clr.pred count_conc
## 1     FALSE      FALSE  FALSE   FALSE   FALSE    FALSE      FALSE
## 2     FALSE      FALSE  FALSE   FALSE   FALSE    FALSE      FALSE
##   count_conc_measured f.int.obs f.int.pred f.obs f.pred kel.iv.obs kel.iv.pred
## 1               FALSE     FALSE      FALSE FALSE  FALSE      FALSE       FALSE
## 2               FALSE     FALSE      FALSE FALSE  FALSE      FALSE       FALSE
##   kel.obs kel.pred lambda.z.n.points_blq mrt.iv.obs mrt.iv.pred mrt.ivmd.obs
## 1   FALSE    FALSE                 FALSE      FALSE       FALSE        FALSE
## 2   FALSE    FALSE                 FALSE      FALSE       FALSE        FALSE
##   mrt.ivmd.pred mrt.md.obs mrt.md.pred mrt.obs mrt.pred thalf.eff.iv.obs
## 1         FALSE      FALSE       FALSE   FALSE    FALSE            FALSE
## 2         FALSE      FALSE       FALSE   FALSE    FALSE            FALSE
##   thalf.eff.iv.pred thalf.eff.obs thalf.eff.pred time_above tobit_residual
## 1             FALSE         FALSE          FALSE      FALSE          FALSE
## 2             FALSE         FALSE          FALSE      FALSE          FALSE
##   vss.iv.obs vss.iv.pred vss.ivmd.obs vss.ivmd.pred vss.md.obs vss.md.pred
## 1      FALSE       FALSE        FALSE         FALSE      FALSE       FALSE
## 2      FALSE       FALSE        FALSE         FALSE      FALSE       FALSE
##   vss.obs vss.pred vz.iv.obs vz.iv.pred vz.obs vz.pred
## 1   FALSE    FALSE     FALSE      FALSE  FALSE   FALSE
## 2   FALSE    FALSE     FALSE      FALSE  FALSE   FALSE
## 
## $allow_partial_missing_units
## [1] FALSE
## 
## $hl_method
## [1] "log-linear"
## 
## $sparse_lambda_z_se
## [1] "delta"
## 
## $tobit_n_points_penalty
## [1] 0
## 
## $tobit_optim_control
## list()
## 
## 
## $columns
## $columns$exclude
## [1] "exclude"
## 
## 
## attr(,"class")
## [1] "PKNCAresults" "list"        
## attr(,"provenance")
## Provenance hash 1010dd656fa2060bf5d457ba131dbe6d generated on 2026-11-11 19:39:58.822118 with R version 4.6.2 (2026-10-29).

summary(results_obj)

##  start end  N     auclast        cmax
##      0  24 12 98.8 [23.0] 8.65 [17.0]
##    144 168 12  115 [28.4] 10.0 [21.0]
## 
## Caption: auclast, cmax: geometric mean and geometric coefficient of variation; N: number of subjects

Bill Denney

Load the data

Merge the Concentration and Dose

Compute the parameters

Multiple Dose Example