A Limited Sampling Model for Estimating Pharmacokinetics of CPT‐11 and Its Metabolite SN‐38

Abstract

The objective of this study was to develop a limited sampling model (LSM) to estimate the area under the curve (AUC) of 7‐ethyl‐10‐[4‐(1‐piperidino)‐1‐piperidino]carbonyloxycamptothecin (CPT‐11) and that of 7‐ethyl‐10‐hydroxycamptothecin (SN‐38) as predictive pharmacokinetic variables for leukopenia and episodes of diarrhea induced by CPT‐11 administration. The model was developed with a training set consisting of pharmacokinetic studies in 36 patients who received a 90‐min i.v. infusion of CPT‐11 at a dose of 100 mg/m2. A multiple regression analysis of CPT‐11 or SN‐38 concentrations observed at each time point in the training set was used to predict the AUC of CPT‐11 or SN‐38. The final sampling models using only two time points were: