Enhancement of oral bioavailability of paclitaxel after oral administration of Schisandrol B in rats

✍ Scribed by Jing Jin; Huichang Bi; Jinqing Hu; Guoping Zhong; Lizi Zhao; Zhiying Huang; Min Huang

• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: English
• Weight: 90 KB
• Volume: 31
• Category: Article
• ISSN: 0142-2782
• DOI: 10.1002/bdd.705

✦ Synopsis

Abstract

Paclitaxel is a substrate of the efflux transporters such as P‐glycoprotein, and is mainly metabolized by the liver. Schisandrol B (Sch B), one of the active components in Schisandra, has been reported to be able to inhibit the activity of P‐gp and CYP3A. It might be possible that Sch B would alter the pharmacokinetic behavior of paclitaxel. Therefore, the purpose of this study was to investigate the effect of Sch B on the pharmacokinetics of paclitaxel administered orally and intravenously in rats. Paclitaxel were administered to rats orally (30 mg/kg) or intravenously (0.5 mg/kg) with or without the concomitant administration of Sch B (10 or 25 mg/kg). Oral pharmacokinetic parameters of paclitaxel were significantly altered when pretreated with Sch B. There were significant increases in AUC~0‐24h~ (from 297.7±110.3 to 838.9±302.1 h*ng/ml; p<0.05) and C~max~ (from 51.7±20.1 to 136.4±35.5 ng/ml; p<0.05) in the presence of Sch B (25 mg/kg). The pharmacokinetic parameters for i.v. paclitaxel were not significantly affected by Sch B in contrast to that of oral administration. Since the presence of Sch B enhanced the systemic exposure of paclitaxel, their pharmacokinetic interaction should be taken into consideration. As the oral bioavailability of paclitaxel was increased about 3‐fold in the presence of Sch B, the concomitant use of Sch B may provide a benefit in the oral delivery of paclitaxel. Copyright © 2010 John Wiley & Sons, Ltd.