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Lack of Effect of Ginkgo biloba on Voriconazole Pharmacokinetics in Chinese Volunteers Identified as CYP2C19 Poor and Extensive Metabolizers

Clinical Researcher, Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, China

Guo Wang, PhD

Post-Doctorate, Institute of Clinical Pharmacology, Central South University

Lian-Sheng Wang, PharmD

Associate Professor, Institute of Clinical Pharmacology, Central South University

Dong-sheng Ou-yang, PharmD

Associate Professor, Institute of Clinical Pharmacology, Central South University

Hao Chen, MS

Research Fellow, Changsha Central Hospital, Changsha

Qing Li, PharmD

Lecturer, Institute of Clinical Pharmacology, Central South University

Wei Zhang, PharmD

Assistant Professor, Institute of Clinical Pharmacology, Central South University

Zhi-Rong Tan, PharmD

Research Fellow, Institute of Clinical Pharmacology, Central South University

Lan Fan, PharmD

Lecturer, Institute of Clinical Pharmacology, Central South University

Yi-Jing He, PharmD

Research Fellow, Institute of Clinical Pharmacology, Central South University

Hong-Hao Zhou, MD

Professor, Institute of Clinical Pharmacology, Central South University

Reprints: Dr. Hong-Hao Zhou, Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, Hunan 410078, China, fax 86-731-2354476, hhzhou2003{at}163.com

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 voriconazole 200 mg after administration of Ginkgo biloba 120 mg twice daily for 12 days 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-) was 5.17 µg·h/mL after administration of voriconazole alone and 4.28 µg·h/mL after voriconazole with Ginkgo biloba (p > 0.05). The other pharmacokinetic parameters of voriconazole such as AUC_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.

Key Words: CYP2C19, genetic polymorphism, Ginkgo biloba, voriconazole

Published Online, March 18, 2009. www.theannals.com, DOI 10.1345/aph.1L537