Induction of propranolol metabolism by Ginkgo biloba extract EGb 761 in rats

Zhao, Li-Zi, Huang, Ming, Chen, Jie, Rachel Ee, Pui Lai, Chan, Eli, Duan, Wei, Guan, Yong-Yuna, Hong, Yun-Han, Chen, Xiao and Zhou, Shufeng 2006, Induction of propranolol metabolism by Ginkgo biloba extract EGb 761 in rats, Current drug metabolism, vol. 7, no. 6, pp. 577-587.

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Title Induction of propranolol metabolism by Ginkgo biloba extract EGb 761 in rats
Author(s) Zhao, Li-Zi
Huang, Ming
Chen, Jie
Rachel Ee, Pui Lai
Chan, Eli
Duan, Wei
Guan, Yong-Yuna
Hong, Yun-Han
Chen, Xiao
Zhou, Shufeng
Journal name Current drug metabolism
Volume number 7
Issue number 6
Start page 577
End page 587
Publisher Bentham Science Publishers Ltd.
Place of publication Hilversum, The Netherlands
Publication date 2006-08
ISSN 1389-2002
1875-5453
Keyword(s) Ginkgo biloba
cytochrome P450
propranolol
rat
Summary Ginkgo biloba is one of the most popular herbal medicines in the world, due to its purported pharmacological effects, including memory-enhancing, cognition-improving, and antiplatelet effects. When used in the elderly, Ginkgo has a high potential for interactions with cardiovascular drugs. This study aimed to investigate the effects of the standard Ginkgo biloba extract (EGB 761) treatment on the pharmacokinetics of propranolol and its metabolism to form Ndesisopropylpropranolol (NDP) in rats. We also examined the activity and expression of cytochrome P450 (CYP) 1A and other CYPs in rats treated with EGb 761 at 10 and 100 mg/kg/day for 10 days. A single oral dose of propranolol (10 mg/kg) was administered on day 11 and the concentrations of both propranolol and NDP were determined using validated liquid chromatography-mass spectrometry (LC-MS) methods. The levels of mRNA and protein of various CYPs were determined by RT-PCR and Western blotting analysis, respectively. Pretreatment of EGb 761 at 100 mg/kg, but not 10 mg/kg, for 10 days significantly reduced the area under the plasma concentration-time curve (AUC) and maximum plasma concentration (C max) of propranolol, whereas those values of NDP were significantly increased. CYP1A1, 1A2, 2B1/2, and 3A1 activities and gene expression in the rat liver were significantly increased in a dose-dependent manner by pretreatment with EGb 761. The ex-vivo formation of NDP in liver microsomes from rats pretreated with EGb 761 was markedly enhanced. The formation of NDP from propranolol in liver microsomes was significantly inhibited by α- naphthoflavone (ANF, a selective CYP1A2 inhibitor), but not by quinidine (a CYP2D inhibitor). These results indicated that EGb 761 pretreatment decreased the plasma concentrations of propranolol by accelerated conversion of parental drug to NDP due to induction of CYP1A2. EGb 761 pretreatment also significantly induced CYP2B1/2 and CYP3A1, suggesting potential interactions with substrate drugs for these two enzymes. Further study is needed to explore the potential for gingko-drug interactions and the clinical impact.
Language eng
Field of Research 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2006, Bentham Science Publishers Ltd.
Persistent URL http://hdl.handle.net/10536/DRO/DU:30009268

Document type: Journal Article
Collection: School of Medicine
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