Omeprazole and lansoprazole are not inducers of cytochrome P4501A2 under conventional therapeutic conditions.
OBJECTIVE
Claims that substituted benzimidazole molecules induce cytochromes P4501A2 are still controversial. This study was undertaken to evaluate their inducing potency under conventional therapeutic conditions.


METHODS
Twelve healthy non-smoking young volunteers were given 20 mg omeprazole or 30 mg lansoprazole daily, in random order, for 2 weeks, separated by a 3 week wash-out period. We evaluated the CYP1A2 activity by the ratio of the molar urinary concentrations (CUM ratio) of the three end products of the paraxanthine demethylation of caffeine over the molar concentration of a paraxanthine 8-hydroxylation product.


RESULTS
This urinary metabolite ratio has previously been shown to be correlated with caffeine clearance. There was slight but non-significant enhancement of the CUM ratio after 2 weeks of treatment with omeprazole (3.62 (1.58) on Day 15 vs 3.09 (1.43) on Day 1), and after lansoprazole (4.26 (2.3) vs 3.65 (2.36)). Similarly, one week of treatment did not significantly alter the CUM ratio after omeprazole or lansoprazole (3.11 (1.58) and 3.28 (1.59), respectively on Day 8).


CONCLUSIONS
The results show that both omeprazole and lansoprazole in the daily recommended therapeutic doses of 20 mg and 30 mg, respectively, have no influence on the metabolism of caffeine, and therefore no influence on cytochrome CYP1A2 activity.
Rizzo
N
N
Pharmacie Hôpital Lariboisière, Paris, France.
Padoin
C
C
Palombo
S
S
Scherrmann
J M
JM
Girre
C
C
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000284:Administration, Oral; D000328:Adult; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002110:Caffeine / Q000378:metabolism; D018592:Cross-Over Studies; D019388:Cytochrome P-450 CYP1A2; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006900:Hydroxylation; D064747:Lansoprazole; D008297:Male; D008745:Methylation; D008875:Middle Aged; D009853:Omeprazole / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D010088:Oxidoreductases / Q000096:biosynthesis*; D054328:Proton Pump Inhibitors
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D004791:Enzyme Inhibitors; D054328:Proton Pump Inhibitors; D064747:Lansoprazole; D002110:Caffeine; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D019388:Cytochrome P-450 CYP1A2; D009853:Omeprazole