Effects of formulation on pharmacokinetics of docetaxel in rats

The aim of this study was to investigate the effects of formulation vehicles on the pharmacokinetics of docetaxel. The following three formulations of docetaxel were prepared to compare the pharmacokinetic profiles of docetaxel: Tween ® 80 formulation (a vehicle composition of Taxotere ® ), Cremophor ® EL formulation (a vehicle composition of Taxol ® ) and DMSO formulation (a combination of surfactants and solvents). Three different formulations of docetaxel were injected into the femoral vein of each rat at a dose of 5 mg/kg. Docetaxel and internal standard (IS, paclitaxel) were extracted from plasma by one-step extraction with acetonitrile. Docetaxel and IS were eluted at 13.0 min and 15.7 min in rat plasma, respectively, without interfering peaks from the endogenous components. Docetaxel was highly distributed to body organs and cleared from the body quickly with a short elimination half-life in Tween ® 80 formulation. In Cremophor ® EL formulation and DMSO formulation, systemic exposure (AUC) and maximum plasma concentration of docetaxel were enhanced 6-fold and 4-fold, respectively, as compared with Tween ® 80 formulation after IV injection. These results suggest that the disposition patterns of docetaxel could be affected by formulation vehicles following IV injection.