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26 février 2011 6 26 /02 /février /2011 11:07

Eur J Clin Pharmacol. 2009 Jun;65(6):601-8. Epub 2009 Jan 27.

Effects of allicin on CYP2C19 and CYP3A4 activity in healthy volunteers with different CYP2C19 genotypes.

Yang LJFan LLiu ZQMao YMGuo DLiu LHTan ZRPeng LHan CTHu DLWang DZhou HH.

Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University, Changsha, Hunan 410078, People's Republic of China.

OBJECTIVE: To investigate the interaction between allicin and omeprazole and to observe the effects of allicin on CYP2C19 and CYP3A4 activity in healthy Chinese male volunteers with different CYP2C19 genotypes.

METHODS: Eighteen subjects (six CYP2C19*1/CYP2C19*1, four CYP2C19*1/CYP2C19*2, two CYP2C19*1/ CYP2C19*3, and six CYP2C19*2/ CYP2C19*2) were enrolled in a two-phase randomized crossover trial. In each phase, all subjects received placebo or a 180 mg allicin capsule once daily for 14 consecutive days. The pharmacokinetics of omeprazole (20 mg orally on day 15) was determined for up to 12 h following administration by high-performance liquid chromatography.

RESULTS: In carriers of the CYP2C19*1/CYP2C19*1 and CYP2C19*1/CYP2C19*2 or *3 genotype, allicin treatment increased the peak plasma concentration (C(max)) of omeprazole by 49.7 +/- 7.2 (p < 0.001) and 54.2 +/- 9.2% (p < 0.001), and increased the area under the plasma time-concentration curve (AUC(0-infinity)) of omeprazole by 48.1 +/- 9.0 (p = 0.001) and 73.6 +/- 26.7% (p < 0.001), respectively. The ratio of AUC(0-infinity) of 5-hydroxyomeprazole to omeprazole (a marker for CYP2C19 activity) decreased significantly (p < 0.001 and p = 0.001, respectively). However, no pharmacokinetic parameters were significantly changed by allicin in CYP2C19*2/CYP2C19*2. The C(max) and AUC(0-infinity) of omeprazole sulfone were unchanged in all three genotypes.

CONCLUSIONS: Allicin reduced the metabolism of omeprazole by inhibiting CYP2C19 activity in individuals with the CYP2C19*1/CYP2C19*1 and CYP2C19*1/CYP2C19*2 or *3 genotypes, but not in those with the CYP2C19*2/ CYP2C19*2 genotype. Allicin did not significantly affect the activity of CYP3A4 in all subjects.

PMID: 19172254 [PubMed - indexed for MEDLINE]

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