Effect of Wuzhi Tablet ( Schisandra sphenanthera extract ) on the Pharmacokinetics of Cyclosporin A in Rats
2012; Wiley; Volume: 27; Issue: 8 Linguagem: Inglês
10.1002/ptr.4849
ISSN1099-1573
AutoresXin‐ping Xue, Xiaoling Qin, Chenshu Xu, Guoping Zhong, Ying Wang, Min Huang, Huichang Bi,
Tópico(s)Drug Transport and Resistance Mechanisms
ResumoIn our previous reports, Wuzhi tablet (an herbal preparation of ethanol extract of Wuweizi ( Schisandra sphenanthera )) can significantly increase the blood concentration of tacrolimus and paclitaxel in rats by inhibiting the CYP3A‐mediated metabolism and the P‐gp‐mediated efflux. Cyclosporin A (CsA), a well‐known immunosuppressant agent, is also a substrate of CYP3A and P‐gp. Therefore, this study aimed to investigate whether and how WZ affects pharmacokinetics of CsA in rats. The AUC 0–48h and C max of CsA were increased by 40.1% and 13.1%, respectively, with a single oral co‐administration of WZ and high dose of CsA (37.8 mg/kg). Interestingly, after a single oral co‐administration of WZ and low dose of CsA (1.89 mg/kg), the AUC 0–36 h and C max of CsA were dramatically increased by 293.1% (from 1103.2 ± 293.0 to 4336.5 ± 1728.3 ng.h/mL; p < 0.05) and 84.1% (from 208.5 ± 67.9 to 383.1 ± 92.5 ng/mL; p < 0.05), respectively. The CL/F was decreased from 1.7 L/h/kg to 0.5 L/h/kg. Thus, the effect of WZ on high dose of CsA was not significant, but pharmacokinetic parameters of CsA at low dose were significantly influenced by co‐administration of WZ. The herb–drug interaction should be taken into consideration at this situation. Copyright © 2012 John Wiley & Sons, Ltd.
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