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

Joon Hee Park, Jung Hyun Park, Hye Jung Hur, Jong Soo Woo, Hwa Jeong Lee

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35 Scopus citations

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 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.

Original languageEnglish
Pages (from-to)296-301
Number of pages6
JournalEuropean Journal of Pharmaceutical Sciences
Volume45
Issue number3
DOIs
StatePublished - 14 Feb 2012

Bibliographical note

Funding Information:
This work was supported by a National Research Foundation of Korea (NRF) Grant funded by the Korean Government (MEST) (NCRC Program: 2011-0006244, Basic Science Research Program: 2011-0005990), by the Korea Healthcare technology R&D Project (A080766) funded by the Ministry for Health, Welfare and Family Affairs and by the Ewha Global Top5 Grant 2011 of Ewha Womans University.

Keywords

  • Bioavailability
  • Microemulsion
  • Paclitaxel
  • Pharmacokinetics
  • Silymarin

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