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Effect of Wuzhi Tablet ( Schisandra sphenanthera extract) on the Pharmacokinetics of Paclitaxel in Rats

2011; Wiley; Volume: 25; Issue: 8 Linguagem: Inglês

10.1002/ptr.3407

1099-1573

Jing Jin, Huichang Bi, Jinqing Hu, Hang Zeng, Guoping Zhong, Lizi Zhao, Zhiying Huang, Min Huang,

Plant-derived Lignans Synthesis and Bioactivity

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. Copyright © 2011 John Wiley & Sons, Ltd.