Lack of Effect of Ginkgo biloba on Voriconazole Pharmacokinetics in Chinese Volunteers Identified as CYP2C19 Poor and Extensive Metabolizers
Lack of Effect of Ginkgo biloba on Voriconazole Pharmacokinetics in Chinese Volunteers Identified as CYP2C19 Poor and Extensive Metabolizers
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DOI：
10.1345/aph.1l537
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发表时间：
2009-04-01
影响因子：
2.9
通讯作者：
Zhou, Hong-Hao
中科院分区：
文献类型：
--
作者：
Lei, He-Ping;Wang, Guo;Zhou, Hong-Hao
背景：银杏是世界上最受欢迎的草药补充剂之一。该补充剂已被证明能诱导参与伏立康唑代谢的主要细胞色素P450同工酶--细胞色素P450的酶活性。由于该酶具有遗传多态性，其诱导作用可能受CYP2C19代谢物状态的调节。目的：研究银杏叶作为CYP2C19的诱导剂对中国志愿者体内伏立康唑单剂量药代动力学的影响。方法：选择14名健康、不吸烟的志愿者--7名CYP2C19广泛代谢物(2C19*1/2C19*1)和7名不良代谢物(2C19*2/2C19*2)--参与本研究。结果：对于广谱代谢药，伏立康唑的血药浓度-时间曲线下面积(AUC(0-无穷))在单用伏立康唑后为5.17 mU g·H/m L，与银杏叶合用后为4.28 u g·H/m L(p>；0.05)。在银杏叶存在下，伏立康唑的其他药动学参数，如AUCo(0-24)、达峰时间、半衰期和表观清除量也没有显著变化。结论：银杏叶制剂治疗12天对伏立康唑的单剂量药代动力学无明显影响，无论是泛代谢物还是不良代谢物。因此，伏立康唑与银杏叶之间的药代动力学相互作用可能具有有限的临床意义。
BACKGROUND: Ginkgo biloba is one of the most popular herbal supplements in the world. The supplement has been shown to induce the enzymatic activity of CYP2C19, the main cytochrome P450 isozyme involved in voriconazole metabolism. Because this enzyme exhibits genetic polymorphism, the inductive effect was expected to be modulated by the CYP2C19 metabolizer status.OBJECTIVE: To examine the possible effects of Ginkgo biloba as an inducer of CYP2C19 on single-dose pharmacokinetics of voriconazole in Chinese volunteers genotyped as either CYP2C19 extensive or poor metabolizers.METHODS: Fourteen healthy, nonsmoking volunteers-7 CYP2C19 extensive metabolizers (2C19*1/2C19*1) and 7 poor metabolizers (2C19*2/2C19*2)-were selected to participate in this study. Pharmacokinetics of oral voriconazo 200 mg after administration of Ginkgo biloba 120 mg twice daily for 12 d ays were determined for up to 24 hours by liquid chromatography-electrospray tandem mass spectrometry in a 2-phase randomized crossover study with 4-week washout between phases.RESULTS: For extensive metabolizers, the median value for voriconazole area under the plasma concentration-time curve from zero to infinity (AUC(0-infinity)) was 5.17 mu g.h/mL after administration of voriconazole alone and 4.28 mu g.h/mL after voriconazole with Ginkgo biloba (p > 0.05). The other pharmacokinetic parameters of voriconazole such as AUCo(0-24), time to reach maximum concentration, half-life, and apparent clearance also did not change significantly for extensive metabolizers in the presence of Ginkgo biloba. Pharmacokinetic parameters followed a similar pattern for poor metabolizers.CONCLUSIONS: The results suggest that 12 days of treatment with Ginkgo biloba did not significantly alter the single-dose pharmacokinetics of voriconazole in either CYP2C19 extensive or poor metabolizers. Therefore, the pharmacokinetic interactions between voriconazole and Ginkgo biloba may have limited clinical significance.