A comparative computer simulation study of three different sparse-sampling methods for the estimation of steady-state...

A limited-sampling method is proposed to estimate the area under the curve (AUC) of concentration versus time and maximum concentration (Cmax) 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 Cmax. 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 Cmax with one or two samples in toxicokinetic studies following single or multiple oral dosing without detailed pharmacokinetic studies.