Omeprazole weakly inhibits CYP1A2 activity in man.

Article Details

Citation

Rost KL, Fuhr U, Thomsen T, Zaigler M, Brockmoller J, Bohnemeier H, Roots I

Omeprazole weakly inhibits CYP1A2 activity in man.

Int J Clin Pharmacol Ther. 1999 Nov;37(11):567-74.

PubMed ID
10584979 [ View in PubMed
]
Abstract

BACKGROUND AND OBJECTIVES: Omeprazole is an inducer of human cytochrome P450 1A (CYP1A) enzymes, but shows inhibitory effects on CYP2C19 and CYP3A4. In this study, a potential inhibitory effect of omeprazole on caffeine metabolism, a validated CYP1A2 marker, was examined. METHODS: A randomized, balanced crossover single-dose study was conducted in 16 healthy volunteers comprising 12 extensive (EM) and 4 poor metabolizers (PM) for CYP2C19. All volunteers received a 40 mg omeprazole dose or placebo 0.5 h prior to caffeine 3 mg/kg body weight. Six EMs were re-tested with 80 mg of omeprazole. In vitro, effects of omeprazole on caffeine N3-demethylation were determined in human liver microsomes. RESULTS: In vivo, non-parametric point estimates (90% confidence intervals) for the ratios of caffeine pharmacokinetics with/without co-administration of the 40 mg omeprazole dose were: AUC 1.08 (1.04 - 1.13), MRT 1.09 (0.99 - 1.19), and plasma ratio of paraxanthine/caffeine 6 h post-dose 0.91 (0.80 - 1.00). Inhibition of caffeine N3-demethylation by omeprazole was slightly more pronounced in PM than in EM of CYP2C19. Estimates for the 80 mg omeprazole dose were: AUC 1.12 (1.05 -1.18), MRT 1.18 (1.07 - 1.30), and paraxanthine/caffeine ratio 0.83 (0.74 -0.94). In vitro, omeprazole was mainly a competitive CYP1A2 inhibitor with K(i) values of around 150 microM. CONCLUSIONS: Omeprazole exerts a concentration-dependent inhibition of CYP1A2 activity in man. However, even after single oral doses up to 80 mg, this effect is weak and without clinical relevance.

DrugBank Data that Cites this Article

Drug Enzymes
DrugEnzymeKindOrganismPharmacological ActionActions
OmeprazoleCytochrome P450 1A2ProteinHumans
Unknown
Inducer
Details
Drug Interactions
DrugsInteraction