title: 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.
authors.affiliation: Center for Cell Signaling & Drug Discovery Research, Division of Life and Pharmaceutical Sciences and College of Pharmacy, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors.forename: Joon Hee
authors.initials: JH
authors.lastname: Park
authors.forename: Jung Hyun
authors.initials: JH
authors.lastname: Park
authors.forename: Hye Jung
authors.initials: HJ
authors.lastname: Hur
authors.forename: Jong Soo
authors.initials: JS
authors.lastname: Woo
authors.forename: Hwa Jeong
authors.initials: HJ
authors.lastname: Lee
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors*; D000284:Administration, Oral; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D004655:Emulsions / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D017239:Paclitaxel / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012838:Silymarin / Q000494:pharmacology*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D004655:Emulsions; D012838:Silymarin; D017239:Paclitaxel