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Effect of Wuzhi Tablet ( Schisandra sphenanthera extract) on the Pharmacokinetics of Paclitaxel in Rats
Author(s) -
Jin Jing,
Bi Huichang,
Hu Jinqing,
Zeng Hang,
Zhong Guoping,
Zhao Lizi,
Huang Zhiying,
Huang Min
Publication year - 2011
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.3407
Subject(s) - paclitaxel , pharmacokinetics , schisandra , pharmacology , chemistry , medicine , chemotherapy , traditional chinese medicine , alternative medicine , pathology
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.