A comparative computer simulation study of three different sparse-sampling methods for the estimation of steady-state area under the concentration-time curve (AUC) and maximum concentration (C-max) in toxicokinetics

A limited-sampling method is proposed to estimate the area under the curve (AUC) of concentration Versus time and maximum concentration (C-max,) following single or multiple oral doses of a hypothetical drug. The plasma concentration versus time data sets for 50 animals were generated by simulation. The limited-sampling model (LSM) was developed with samples from 10 animals at a single time point. The model was validated in another 40 animals who received either a 500-mg single dose or multiple doses orally. The model provided good population mean estimates of AUC and C-max. The proposed method was compared with the existing two methods; they are, naive sampling (five time points) and optimal sampling (three time points). The method described here may be useful in estimating AUC and C-max with one or two samples in toxicokinetic studies following single or multiple oral dosing without detailed pharmacokinetic studies.