Effects of silymarin and formulation on the oral bioavailability of paclitaxel in rats

Abstract

The aims of the present study were to investigate the effects of silymarin, an inhibitor of the P-glycoprotein efflux pump, on oral bioavailability of paclitaxel in rats, and to compare pharmacokinetic parameters of paclitaxel between a commercial formulation of paclitaxel (Taxol®) and a paclitaxel microemulsion. Oral bioavailability of paclitaxel in a Taxol® formulation was enhanced in the combination with silymarin (10 and 20mg/kg). In particular, the mean maximum plasma concentration (C(max)) and the mean area under the plasma concentration-time curve (AUC(0-)(t)) of paclitaxel in the Taxol® formulation were significantly increased 3-fold and 5-fold compared with control, respectively, following oral co-administration with 10mg/kg of silymarin (p<0.01). When the paclitaxel microemulsion was co-administered with silymarin (20mg/kg) orally, it caused a maximum increase in the absolute bioavailability of paclitaxel (19%). In addition, the relative bioavailability of the paclitaxel microemulsion was 184% as compared to Taxol® after oral dosing, whereas the mean time required to reach C(max) (T(max)) of paclitaxel was decreased in the microemulsion formulation compared with Taxol®, suggesting faster absorption. Based on these results, we conclude that oral bioavailability of paclitaxel is significantly improved by co-administration with silymarin, an inhibitor of the P-gp efflux pump and by microemulsion formulation.