Four-week treatment with omeprazole increases the metabolism of caffeine.
OBJECTIVE
It has been suggested that omeprazole is an inducer of the cytochrome P450 1A, both in vitro and in vivo. To evaluate whether omeprazole treatment might affect the activity of P450 1A2, we performed a study of caffeine metabolism, which is mainly via P450 1A.


METHODS
Thirteen subjects (one healthy volunteer and 12 patients) who were treated with omeprazole, 20 mg each morning for 4 wk, and a control group of 13 healthy volunteers, participated in the study. A test of caffeine metabolism was performed before treatment, 28 days after beginning treatment and, whenever possible, 28 days after treatment. Blood samples were analyzed for theobromine, paraxanthine, and theophylline, by high performance liquid chromatography.


RESULTS
P4501A2 activity was determined as the ratio of (paraxanthine + theobromine + theophylline)/(metabolites + caffeine) which represents the total caffeine N-oxidative demethylations; this ratio was expressed as a percentage. For patients, on day 0, the percentage of total metabolism was 34.3% +/- 8.3; on day 28, it was 42.7% +/- 10.8; the difference was statistically significant (p < 0.01). No intra-individual variation of P450 1A2 activity was observed in the control group.


CONCLUSIONS
These results demonstrate that omeprazole increases the metabolism of caffeine, especially N-1 and N-3 demethylation pathways, after 28 days of treatment with omeprazole, and suggest that omeprazole, when used for this period, is an inducer of hepatic cytochrome P4501A2.
Nousbaum
J B
JB
Service d'Hépato-gastroentérologie, Centre Régional de Pharmacovigilance, CHRU Morvan, Brest, France.
Berthou
F
F
Carlhant
D
D
Riche
C
C
Robaszkiewicz
M
M
Gouerou
H
H
D002110:Caffeine / Q000378:metabolism*; D019388:Cytochrome P-450 CYP1A2; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000187:drug effects; D004790:Enzyme Induction; D004941:Esophagitis / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D008099:Liver / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D009853:Omeprazole / Q000494:pharmacology / Q000627:therapeutic use*; D010088:Oxidoreductases / Q000096:biosynthesis* / Q000187:drug effects; D010437:Peptic Ulcer / Q000188:drug therapy* / Q000378:metabolism; D013997:Time Factors
D002110:Caffeine; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D019388:Cytochrome P-450 CYP1A2; D009853:Omeprazole