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Effects of silymarin and formulation on the oral bioavailability of paclitaxel in rats
- Effects of silymarin and formulation on the oral bioavailability of paclitaxel in rats
- Park J.H.; Hur H.J.; Woo J.S.; Lee H.J.
- Ewha Authors
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- European Journal of Pharmaceutical Sciences
- European Journal of Pharmaceutical Sciences vol. 45, no. 3, pp. 296 - 301
- SCI; SCIE; SCOPUS
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- 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 20 mg/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 10 mg/kg of silymarin (p < 0.01). When the paclitaxel microemulsion was co-administered with silymarin (20 mg/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. © 2011 Elsevier B.V. All rights reserved.
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