Inhibition of paclitaxel elimination in the isolated perfused rat liver by Cremophor el

Abstract

Purpose: Cremophor can alter the pharmacokinetics of cytotoxic drugs, including doxorubicin and etoposide. In view of its presence in the formulation of paclitaxel, the aim of this study was to investigate the influence of Cremophor on the hepatobiliary elimination of paclitaxel. Methods: In a recirculating isolated perfused rat-liver system the elimination of 1.7 mg paclitaxel given as a bolus into the perfusate reservoir was monitored in perfusate and bile in controls and after the administration of either 80 or 800 μl Cremophor. The higher dose of Cremophor yields clinically relevant perfusate concentrations. Paclitaxel was measured in perfusate, bile, and liver tissue by high-performance..