Comparative in vitro properties and clinical pharmacokinetics of paclitaxel following the administration of taxol® and paxene®

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 were 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.