A population pharmacokinetic analysis of ixabepilone in patients with cancer

Abstract

2521 Background: Ixabepilone, the first in a new class of antimicrotubule agents: the epothilones, is indicated in the US for the treatment of resistant/refractory metastatic breast cancer (MBC). Mass balance studies found metabolism is the major elimination mechanism. A population pharmacokinetic (PK) analysis was performed to characterize the extent and variability of ixabepilone exposure in cancer patients and to evaluate the influence of selected categorical and continuous covariates on exposure. Methods: Data were collected from 12 monotherapy studies (2 phase I; 10 disease-specific phase II [MBC, localized breast cancer, non-small-cell lung cancer, colorectal cancer, gastric adenocarcinoma, melanoma, and small-cell lung cancer]). The dataset included 4540 observations from 674 patients (128 from phase I; and 546 from phase II) who were given intravenous ixabepilone doses ranging between 1 and 65 mg/m2. Ixabepilone PK was characterized by a compartmental nonlinear mixed-effects model. Results: Ixabep...