Pantoprazole lacks induction of CYP1A2 activity in man.
OBJECTIVE
This drug-drug interaction study investigated the potential influence of the proton pump inhibitor pantoprazole on the CYP1A2 activity as assessed by urinary excretion of caffeine metabolites.


METHODS
12 healthy, non-smoking volunteers underwent two treatment periods of 7 days each in randomized order with once-daily oral intake of 40 mg pantoprazole (test) or placebo (reference). On days 6 and 7 of both periods, 200 mg caffeine was administered two hours after pantoprazole intake, i.e. at the expected t(max) of pantoprazole serum concentrations. Urinary excretion of the caffeine metabolites 1X, 1U, AFMU, 17U was measured up to 8 hours after caffeine intake. In accordance with recent guidelines on drug-drug interactions, lack of interaction was handled as an equivalence problem.


RESULTS
Point estimate and 90% confidence intervals (CI) of the respective ratios test/reference were 0.91 (0.81, 1.03) for (1X + 1U + AFMU)/17U, indicative for CYP1A2 activity, 1.03 (0.94, 1.13) for AFMU/1X (N-acetyl transferase activity) and 1.01 (0.94, 1.09) for 1U/1X (xanthine oxidase activity).


CONCLUSIONS
Pantoprazole does not induce CYP1A2 activity, consistent with previous findings following theophylline administration, nor does it have any influence on N-acetyl-transferase or xanthine oxidase activity.
Hartmann
M
M
Byk Gulden Pharmaceuticals, Konstanz, Germany.
Zech
K
K
Bliesath
H
H
Steinijans
V W
VW
Koch
H
H
Wurst
W
W
Mascher
H
H
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D001562:Benzimidazoles / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D002110:Caffeine / Q000378:metabolism*; D000697:Central Nervous System Stimulants / Q000378:metabolism*; D018592:Cross-Over Studies; D019388:Cytochrome P-450 CYP1A2 / Q000187:drug effects* / Q000378:metabolism; D004311:Double-Blind Method; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D008297:Male; D009853:Omeprazole / Q000031:analogs & derivatives; D000077402:Pantoprazole; D054328:Proton Pump Inhibitors; D013454:Sulfoxides / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D014969:Xanthine Oxidase / Q000378:metabolism
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D001562:Benzimidazoles; D000697:Central Nervous System Stimulants; D004791:Enzyme Inhibitors; D054328:Proton Pump Inhibitors; D013454:Sulfoxides; D002110:Caffeine; D000077402:Pantoprazole; D019388:Cytochrome P-450 CYP1A2; D014969:Xanthine Oxidase; D009853:Omeprazole