Nonlinear pharmacokinetics of paclitaxel in ovarian cancer patients

Abstract

Aim: To characterize the disposition of paclitaxel in patients with ovarian carcinoma after a 3-h infusion.

Methods: Fifteen patients with advanced ovarian cancer were enrolled and were administered paclitaxel in a 3-h infusion at dosing levels of 135 mg/m2, 175 mg/m2, and 235 mg/m2. Thirteen plasma samples were obtained during the infusion and up to 24 h after the infusion. Paclitaxel concentrations in plasma were determined by HPLC assay. Pharmacokinetic parameters were assessed with noncompartment model and model-dependent method.

Results: The disposition of paclitaxel in patients with ovarian cancer conformed to a two-compartment model. The main pharmacokinetic parameters of three groups were T1/2 beta (5.18 +/- 3.49), (6.26 +/- 2.21), and (6.99 +/- 1.45) h, AUC (14.71 +/- 0.76), (39.09 +/- 13.10), and (66.52 +/- 12.23) mg.h.L-1, Cl (14.29 +/- 0.74), (7.52 +/- 2.15), and (6.25 +/- 1.93) L.h-1, respectively.

Conclusion: The disposition of paclitaxel was nonlinear after a 3-h infusion. There was individual variability of metabolism among patients.