title: Effect of Wuzhi tablet (Schisandra sphenanthera extract) on the pharmacokinetics of paclitaxel in rats.
abstract: Wuzhi tablet (WZ, registration no. in China: Z20025766) is a preparation of an ethanol herb extract of Wuweizi (Schisandra sphenanthera) containing 7.5 mg Schisantherin A per tablet. It was reported recently that WZ could significantly increase the blood concentrations of tacrolimus, which might be due to the inhibitory effect of WZ and its ingredients on P-gp and/or CYP450 activity. Paclitaxel is a substrate of the efflux transporter P-gp, and is mainly metabolized by CYP450 enzymes in the liver. Therefore, the purpose of this study was to investigate whether and how WZ affects the pharmacokinetics of paclitaxel in rats. After pretreatment with WZ, there were significant increases in the AUC(0-24h) of oral paclitaxel (from 280.8 ± 97.3 to 543.5 ± 115.2 h ng/mL; p < 0.05) and C(max) (from 44.6 ± 16.4 to 86.8 ± 16.1 ng/mL; p < 0.05). The pharmacokinetic data for i.v. paclitaxel with WZ showed a relatively small (when compared against oral paclitaxel) but still significant increase in AUC(0-24h) (from 163.6 ± 22.1 to 212.7 ± 17.7 h ng/mL; p < 0.05) and a decrease in clearance (from 3.2 ± 0.6 to 2.2 ± 0.3 L/h/kg; p < 0.05). Thus, the presence of WZ improved the systemic exposure of paclitaxel in rats. The herb-drug interaction between WZ and paclitaxel should be taken into consideration in clinical use.
authors.affiliation: School of Pharmaceutical Science, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Jin
authors.forename: Huichang
authors.initials: H
authors.lastname: Bi
authors.forename: Jinqing
authors.initials: J
authors.lastname: Hu
authors.forename: Hang
authors.initials: H
authors.lastname: Zeng
authors.forename: Guoping
authors.initials: G
authors.lastname: Zhong
authors.forename: Lizi
authors.initials: L
authors.lastname: Zhao
authors.forename: Zhiying
authors.initials: Z
authors.lastname: Huang
authors.forename: Min
authors.initials: M
authors.lastname: Huang
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics*; D002681:China; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D041743:Herb-Drug Interactions; D008297:Male; D017239:Paclitaxel / Q000493:pharmacokinetics*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D032141:Schisandra / Q000737:chemistry*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal; D010936:Plant Extracts; D017239:Paclitaxel