Pharmacogenetics and herb-drug interactions: experience with Ginkgo biloba and omeprazole.
OBJECTIVE
Ginkgo biloba was found to exert a significant inductive effect on CYP2C19 activity. This study was designed to investigate the potential herb-drug interaction between G. biloba and omeprazole, a widely used CYP2C19 substrate, in subjects with different CYP2C19 genotypes.


METHODS
Eighteen healthy Chinese subjects previously genotyped for CYP2C19 were selected. All subjects received a single omeprazole 40 mg at baseline and then at the end of a 12-day treatment period with G. biloba (140 mg, bid). Multiple blood samples were collected over 12 h, and 24 h urine was collected post omeprazole dosing. Plasma and urine concentrations of omeprazole and its metabolites, 5-hydroxyomeprazole and omeprazole sulfone, were determined, and their pharmacokinetics calculated non-compartmentally.


RESULTS
Plasma concentrations of omeprazole and omeprazole sulfone were significantly decreased, and 5-hydroxyomeprazole significantly increased following G. biloba administration in comparison to baseline. A significant decrease in the ratio of area under the plasma concentration-time curve (AUC) of omeprazole to 5-hydroxyomeprazole was observed in the homozygous extensive metabolizers, heterozygous extensive metabolizers, and poor metabolizers, respectively. The decrease was greater in PMs than EMs. No significant changes in the AUC ratios of omeprazole to omeprazole sulfone were observed. Renal clearance of 5-hydroxyomeprazole was significantly decreased after G. biloba, but the change was not significantly different among the three genotype groups.


CONCLUSIONS
Our results show that G biloba can induce omeprazole hydroxylation in a CYP2C19 genotype-dependent manner and concurrently reduce the renal clearance of 5-hydroxyomeprazole. Co-administration of G. biloba with omeprazole or other CYP2C19 substrates may significantly reduce their effect, but further studies are warranted.
Yin
Ophelia Q P
OQ
School of Pharmacy, the Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
Tomlinson
Brian
B
Waye
Mary M Y
MM
Chow
Albert H L
AH
Chow
Moses S S
MS
D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000097:blood / Q000378:metabolism*; D044466:Asian People; D065731:Cytochrome P-450 CYP2C19; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D020441:Ginkgo biloba; D041743:Herb-Drug Interactions; D006801:Humans; D008297:Male; D006899:Mixed Function Oxygenases / Q000097:blood / Q000378:metabolism*; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000652:urine; D010597:Pharmacogenetics; D010936:Plant Extracts / Q000494:pharmacology; D013997:Time Factors
D004791:Enzyme Inhibitors; D010936:Plant Extracts; C040450:omeprazole sulfone; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole