Pharmacokinetics of combined doxorubicin and paclitaxel in mice

Doxorubicin (DOX) has excellent antitumor activity when combined with paclitaxel (PTX) and this combination is used as first-line treatment for metastatic breast cancer. Results from clinical studies on pharmacokinetic interaction of these agents are not conclusive and pre-clinical studies are still needed. Pharmacokinetic studies were carried out in female Balb/c mice with combined DOX (6 mg/kg) and PTX (10 mg/kg) treatment. Combined treatment with PTX and DOX leads to alterations in the pharmacokinetics of both agents, with the predominant effect being elevated drug levels in liver and gut tissues. DOX levels in kidney and heart tissues were unaffected by concurrent PTX treatment. Further, plasma levels of DOX are not changed by concurrent PTX treatment suggesting that monitoring of plasma levels of DOX, when used in combination with another drug that is a P-glycoprotein (PGP) substrate, will not reflect actual pharmacokinetic changes occurring in other tissues.