Population pharmacokinetics of doxorubicin in Indian cancer patients using NONMEM

Abstract

The population pharmacokinetics of doxorubicin were evaluated based on a mixed-effect model using the NONMEM (VI) program. Doxorubicin in plasma was measured using high-performance liquid chromatography. Plasma concentration measurements (85 plasma samples) of doxorubicin from 28 patients with cancer receiving doxorubicin (with other co-medication) ranging from 20–120 mg by infusion over 1–2 h were analyzed according to a two-compartment model both in FO and FOCE methods. Additive proportional error model was used to describe inter-individual and residual variability. The influence of covariates such as age, body surface area, gender, and clinical laboratory values (SGOT, SGPT) on total body clearance (CL) and volume of distribution (Vd) were examined. No covariate was found to affect the CL and Vd of unchanged doxorubicin. The CL and Vd estimated by FO method were 1.42 L/h and 51.1 L, respectively, and FOCE method are 1.43 L/h and 51.4 L, respectively. The inter-individual variability for CL and Vd and residual variability were 45.8%, 36%, and 12.6%, respectively. The population means and inter-individual and residual variability of pharmacokinetics of doxorubicin were evaluated using the NONMEM program. The results of this study show that the population pharmacokinetic approach could be useful to manage doxorubicin cardio toxicity using sparse data in a clinical setting.