A COMPARATIVE COMPUTER-SIMULATION STUDY OF 3 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 c urve (AUC) of concentration Versus time and maximum concentration (C-m ax,) following single or multiple oral doses of a hypothetical drug. T he plasma concentration versus time data sets for 50 animals were gene rated by simulation. The limited-sampling model (LSM) was developed wi th samples from 10 animals at a single time point. The model was valid ated in another 40 animals who received either a 500-mg single dose or multiple doses orally. The model provided good population mean estima tes of AUC and C-max. The proposed method was compared with the existi ng two methods; they are, naive sampling (five time points) and optima l sampling (three time points). The method described here may be usefu l in estimating AUC and C-max with one or two samples in toxicokinetic studies following single or multiple oral dosing without detailed pha rmacokinetic studies.