Calculate the mean residence time (MRT) for single-dose data or linear multiple-dose data.
Source:R/pk.calc.simple.R
pk.calc.mrt.RdCalculate the mean residence time (MRT) for single-dose data or linear multiple-dose data.
Usage
pk.calc.mrt(auc, aumc)
pk.calc.mrt.iv(auc, aumc, duration.dose)
pk.calc.mrt.md(auctau, aumctau, aucinf, tau)
pk.calc.mrt.md.iv(auctau, aumctau, aucinf, tau, duration.dose)Arguments
- auc
the AUC from 0 to infinity or 0 to tau
- aumc
the AUMC from 0 to infinity or 0 to tau
- duration.dose
The duration of the dose (usually an infusion duration for an IV infusion)
- auctau
the AUC from time 0 to the end of the dosing interval (tau).
- aumctau
the AUMC from time 0 to the end of the dosing interval (tau).
- aucinf
the AUC from time 0 to infinity (typically using single-dose data)
- tau
The dosing interval
Details
mrt is aumc/auc - duration.dose/2 where duration.dose = 0 for oral administration.
mrt.md is aumctau/auctau + tau*(aucinf-auctau)/auctau and should
only be used for multiple dosing with equal intervals between doses.
Note that if aucinf == auctau (as would be the assumption with
linear kinetics), the equation becomes the same as the single-dose MRT.
These are the parameters to use when PK are nonlinear. With linear PK,
MRT and Vss can be measured from a single dose and the single-dose
parameters (mrt.obs, vss.obs, and similar) describe steady state as
well. When PK are nonlinear they do not, so MRT and Vss have to be
measured over a steady-state dosing interval, which is what these
parameters do. The ratio aumctau/auctau on its own (mrt.last over a
dosing interval) is not MRT at steady state and underestimates it
substantially; the tau*(aucinf-auctau)/auctau term accounts for the drug
still in the body at the end of the interval.
Within pk.nca(), tau is detected from the dose times of the group with
find.tau(). When the dosing data hold a single dose (a common
steady-state design where only the profiled dose is recorded), nothing
repeats and nothing can be detected, so give tau as a column of the
interval specification instead; a tau column always takes precedence
over detection. If tau can be neither given nor detected, the parameter
is NA with a warning.
mrt.ivmd is mrt.md less half of the infusion duration, the same
correction that mrt.iv applies to the single-dose MRT. Without it, MRT
and everything derived from it are high by duration.dose/2.