Enhancement of oral bioavailability of paclitaxel after oral administration of Schisandrol B in rats.
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.
Jin
Jing
J
School of Pharmaceutical Science, Sun Yat-sen University, Guangzhou, People's Republic of China.
Bi
Huichang
H
Hu
Jinqing
J
Zhong
Guoping
G
Zhao
Lizi
L
Huang
Zhiying
Z
Huang
Min
M
D000284:Administration, Oral; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D034242:Cyclooctanes / Q000008:administration & dosage / Q000494:pharmacology*; D004149:Dioxoles; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007275:Injections, Intravenous; D017705:Lignans / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D017239:Paclitaxel / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D032141:Schisandra / Q000737:chemistry
D000972:Antineoplastic Agents, Phytogenic; D034242:Cyclooctanes; D004149:Dioxoles; D017705:Lignans; C033585:schizandrol B; D017239:Paclitaxel