EFFECT OF THE PACLITAXEL VEHICLE, CREMOPHOR EL, ON THE PHARMACOKINETICS OF DOXORUBICIN AND DOXORUBICINOL IN MICE

The effect of the paclitaxel vehicle Cremophor on the pharmacokinetics of doxorubicin and doxorubicinol was studied in two groups of mice gi ven intravenously either 2.5 ml kg(-1) Cremophor or saline followed 5 min later by 10 mg kg(-1) doxorubicin. In each group three mice were s acrificed at ten time points and doxorubicin and doxorubicinol were me asured in plasma by high-performance liquid chromatography (HPLC). Wit h Cremophor present, doxorubicin AUC increased from 1420 +/- 440 to 27 70 +/- 660 ng h ml(-1) (P < 0.05) and doxorubicinol AUC increased From 130 +/- 76 to 320 +/- 88 ng h ml(-1) (P < 0.05). Neither the terminal elimination half-lives nor the doxorubicinol-doxorubicin AUC ratio ch anged in the presence of Cremophor, suggesting lack of a direct effect on drug metabolism. The possibility exists that Cremophor may change the pharmacokinetics of both paclitaxel and other drugs given concurre ntly.