Lack of effect of Ginkgo biloba on voriconazole pharmacokinetics in Chinese volunteers identified as CYP2C19 poor and extensive metabolizers.
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-)(infinity)) was 5.17 microg.h/mL after administration of voriconazole alone and 4.28 microg.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.
Lei
He-Ping
HP
Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, China.
Wang
Guo
G
Wang
Lian-Sheng
LS
Ou-yang
Dong-sheng
DS
Chen
Hao
H
Li
Qing
Q
Zhang
Wei
W
Tan
Zhi-Rong
ZR
Fan
Lan
L
He
Yi-Jing
YJ
Zhou
Hong-Hao
HH
D000293:Adolescent; D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D044466:Asian People / Q000235:genetics; D018592:Cross-Over Studies; D065731:Cytochrome P-450 CYP2C19; D004347:Drug Interactions / Q000235:genetics; D004790:Enzyme Induction / Q000235:genetics; D020441:Ginkgo biloba / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D008297:Male; D008517:Phytotherapy / Q000379:methods; D011110:Polymorphism, Genetic; D011743:Pyrimidines / Q000097:blood / Q000493:pharmacokinetics*; D014230:Triazoles / Q000097:blood / Q000493:pharmacokinetics*; D065819:Voriconazole; D055815:Young Adult
D011743:Pyrimidines; D014230:Triazoles; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D065819:Voriconazole