CPT-11 - POPULATION PHARMACOKINETIC MODEL AND ESTIMATION OF PHARMACOKINETICS USING THE BAYESIAN METHOD IN PATIENTS WITH LUNG-CANCER

In this study, we aimed to develop a population pharmacokinetic model for CPT-11 and to use the Bayesian method to estimate CPT-11 pharmacok inetic parameters in each of 43 patients who received combined therapy consisting of CPT-11 and etoposide. The group was divided into first and second data sets of 30 and 13 patients, respectively. We developed a population pharmacokinetic model of CPT-11 based on the first data set. The individual pharmacokinetic parameters [area under the concent ration curve (AUC) and clearance (CL)] were subsequently estimated by using the Bayesian method on the second data set. Plasma CPT-11 concen trations were measured by high-performance liquid chromatography, and compartmental pharmacokinetic models were fitted by the Bayesian metho d. The population pharmacokinetic model was developed by using the non linear mixed effect model. We selected the volume of the central compa rtment (Vc), CL, and distribution rate constants (K12, K21) as populat ion pharmacokinetic parameters. The population mean values (CV%) of Vc , CL, K12, and K21 were, respectively, 31.8 (15.7%) liter/m(2), 14.1 ( 27.8%) liter/h/m(2), 1.1 (8.4%)/h, and 0.41 (30.3%)/h. Residual intrai ndividual variability was 22.9%. The optimal sampling regime for estim ation of the AUC and CL in using the Bayesian method was the two time points of 1 and 8 h post infusion. The mean predictive error, the mean absolute predictive error, and the root mean squared error were -3.3, 9.4, 3.2% (AUC) and 6.3, 10.0, 3.5% (CL), respectively. We concluded that the AUC and CL of CPT-11 could be estimated from plasma concentra tions at two times by using the Bayesian method.