Omeprazole induces hepatic cytochrome P-4501A2. In a previous study th
is effect was shown to be significant in vivo in 6 poor metabolizers,
including 1 intermediate metabolizer, but not in 12 extensive metaboli
zers of S-mephenytoin after 7 days of treatment with 40 mg/day omepraz
ole. In this study, the specificity of the inducing potential of omepr
azole was investigated in these volunteers. Furthermore, in eight of t
he extensive metabolizers the dose dependence of cytochrome P-450 1A2
induction was evaluated. Cytochrome P-450 1A2 activity was monitored b
y means of the C-13-[N3-methyl]caffeine breath test and by means of pl
asma caffeine clearance before omeprazole treatment with 120 mg/day, o
n the seventh day of dosage and after a 7-day washout. Omeprazole plas
ma 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 measure
d on the same study days in all study groups (n = 26). In the eight ex
tensive metabolizers the breath test indicated a dose-dependent increa
se 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 w
as increased by 31.6% +/- 20.7% (p < 0.001) with the higher dose. None
of the study groups exhibited a significant increase of gamma-glutamy
ltransferase activity or urinary excretion of D-glucaric acid or 6 bet
a-hydroxycortisol. This was in contrast to the phenobarbital-type indu
ction observed after treatment with antiepileptic drugs. Induction by
omeprazole seems to be restricted to cytochrome P-450 1A enzymes. Thus
cytochrome P-450 1A2 induction is not clinically relevant with common
therapeutic doses in EMs but might be of relevance after extraordinar
ily high doses or in poor metabolizers of S-mephenytoin.