Effects of clarithromycin on the metabolism of omeprazole in relation to CYP2C19 genotype status in humans

Citation
T. Furuta et al., Effects of clarithromycin on the metabolism of omeprazole in relation to CYP2C19 genotype status in humans, CLIN PHARM, 66(3), 1999, pp. 265-274
Citations number
41
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology,"Pharmacology & Toxicology
Journal title
CLINICAL PHARMACOLOGY & THERAPEUTICS
ISSN journal
0009-9236 → ACNP
Volume
66
Issue
3
Year of publication
1999
Pages
265 - 274
Database
ISI
SICI code
0009-9236(199909)66:3<265:EOCOTM>2.0.ZU;2-U
Abstract
Background and purpose: A triple therapy with omeprazole, amoxicillin (INN, amoxicilline), and clarithromycin is widely used for the eradication of He licobacter pylori. Omeprazole and clarithromycin are metabolized by CYP2C19 and CPP3A4. This study aimed to elucidate whether clarithromycin affects t he metabolism of omeprazole, Methods: After administration of placebo or 400 mg clarithromycin twice a d ay for 3 days, 20 mg omeprazole and placebo or 400 mg clarithromycin were a dministered to 21 healthy volunteers. Plasma concentrations of omeprazole a nd clarithromycin and their metabolites were determined before and 1, 2, 3, 5, 7, 10, and 24 hours after dosing. CYP2C19 genotype status was determine d by a polymerase chain reaction-restriction fragment length polymorphism ( PCR-RFLP) method. Results: Subjects were classified into three groups on the basis of PCR-RFL P analyses for CYP2C19: homozygous extensive metabolizer group (n = 6), het erozygous extensive metabolizer group (n = 11), and poor metabolizer group (n = 4), Mean area under the plasma concentration-time curves from 0 to 24 hours (AUC) of omeprazole in the homozygous extensive metabolizer, heterozy gous extensive metabolizer, and poor metabolizer groups were significantly increased by clarithromycin from 383.9 to 813,1, from 1001.9 to 2110.4, and from 5589.7 to 13098.6 ng . h/mL, respectively. There were significant dif ferences in the mean AUC values of clarithromycin among the three groups. Conclusion: Clarithromycin inhibits the metabolism of omeprazole. Drug inte raction between clarithromycin and omeprazole may underlie high eradication rates achieved by triple therapy with omeprazole, amoxicillin, and clarith romycin.