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Effect of Ginkgo Biloba Extract on the Pharmacokinetics and Metabolism of Clopidogrel in Rats

Deng, Ying, Mo, Yu‐fei, Chen, Xin‐meng, Zhang, Lv‐zhao, Liao, Chao‐feng, Song, Yu, Xu, Chenshu
Phytotherapy research 2016 v.30 no.11 pp. 1886-1892
Ginkgo biloba, biotransformation, cerebrovascular disorders, dose response, in vitro studies, liver microsomes, medicine, metabolites, pharmacokinetics, rats
Ginkgo biloba extract (GBE), a traditional herbal product used worldwide as both medicine and supplement, is often supplied with clopidogrel for the treatment of cerebrovascular diseases. The aim of the current study was to explore the effect of GBE on the metabolism and pharmacokinetics of clopidogrel. The in vitro study using rat liver microsomes revealed that GBE significantly induced the conversion of clopidogrel into its active metabolite. The effect of GBE on the pharmacokinetics of clopidogrel was also investigated in vivo. Compared to rats without GBE pretreatment, administration of 4 mg/kg, 20 mg/kg, and 100 mg/kg of GBE significantly decreased the Cₘₐₓ and the AUC₀–∞ of clopidogrel in a dose‐dependent manner. As expected, pretreatment of high dose GBE significantly increased the Cₘₐₓ and AUC₀–∞ of the clopidogrel active metabolite. However, no marked change was observed following medium and low dose of GBE, suggesting that the biotransformation of clopidogrel was altered differently by high dose of GBE. Our study suggested that the awareness of the potential herb–drug interactions between GBE and clopidogrel should be increased in clinical practice. Copyright © 2016 John Wiley & Sons, Ltd.