Comparative in vitro properties and clinical pharmacokinetics of paclitaxel following the administration of Taxol® and Paxene®

Abstract

Purpose: Taxol® contains paclitaxel formulated in Cremophor EL-P (CrEL-P) and ethanol. Paxene® is similar to Taxol, except for the use of Cremophor EL (CrEL) and the addition of citric acid. Here, we investigated the physicochemical properties and clinical pharmacokinetics of the two paclitaxel formulations. Experimental Design: The size and modality of distribution of CrEL-P and CrEL micelles was determined by dynamic-light scattering. The effect of vehicle composition on the fraction unbound paclitaxel in vitro was determined by equilibrium dialysis. Paclitaxel pharmacokinetics was studied in 61 cancer patients receiving Taxol and 26 patients receiving Paxene. Comparative pharmacokinetics of CrEL-P and CrEL were obtained in 14 and 6 patients, respectively. Results: The size of micelles present in Taxol was slightly smaller (9 to 13%) than those present in Paxene. Surface tension and critical micellar concentration were also similar for the two formulations, with mean values of 37.0 and 38.1 mN/m and 0.0387 and 0.0307 mg/mL, respectively. The fraction unbound paclitaxel was not significantly different for Taxol and Paxene (P > 0.05). Over the tested dose range, the mean clearance of paclitaxel decreased from 45.1 to 16.9 L/h for Taxol, and from 50.7 to 16.4 L/h for Paxene (P > 0.05). Concentrations of the excipient following the administration of CrEL-P or CrEL were also similar. Conclusion: The differences in formulation between Taxol and Paxene do not significantly affect micelle formation and/or quantitative aspects of the vehicle-paclitaxel interaction in vitro and in vivo.