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  • Title: Specific and dose-dependent enzyme induction by omeprazole in human beings.
    Author: Rost KL, Brösicke H, Heinemeyer G, Roots I.
    Journal: Hepatology; 1994 Nov; 20(5):1204-12. PubMed ID: 7927253.
    Abstract:
    Omeprazole induces hepatic cytochrome P-4501A2. In a previous study this effect was shown to be significant in vivo in 6 poor metabolizers, including 1 intermediate metabolizer, but not in 12 extensive metabolizers of S-mephenytoin after 7 days of treatment with 40 mg/day omeprazole. In this study, the specificity of the inducing potential of omeprazole was investigated in these volunteers. Furthermore, in eight of the extensive metabolizers the dose-dependence of cytochrome P-450 1A2 induction was evaluated. Cytochrome P-450 1A2 activity was monitored by means of the 13C-[N3-methyl]caffeine breath test and by means of plasma caffeine clearance before omeprazole treatment with 120 mg/day, on the seventh day of dosage and after a 7-day washout. Omeprazole plasma concentration was measured. Results were compared with those after 40 mg. gamma-Glutamyltransferase activity in serum, as well as urinary excretion of D-glucaric acid and 6 beta-hydroxycortisol, were measured on the same study days in all study groups (n = 26). In the eight extensive metabolizers the breath test indicated a dose-dependent increase of cytochrome P-450 1A2 activity of 8.5% +/- 15.0% (40 mg, mean +/- SD, NS) and 27.2% +/- 16.5% (120 mg, p = 0.002). Caffeine clearance was increased by 31.6% +/- 20.7% (p < 0.001) with the higher dose. None of the study groups exhibited a significant increase of gamma-glutamyltransferase activity or urinary excretion of D-glucaric acid or 6 beta-hydroxycortisol. This was in contrast to the phenobarbital-type induction observed after treatment with antiepileptic drugs. Induction by omeprazole seems to be restricted to cytochrome P-450 1A enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)
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