Pharmacokinetics and effect on caffeine metabolism of the proton pump inhibitors, omeprazole, lansoprazole, and pantoprazole.
OBJECTIVE
To study the pharmacokinetics of three proton pump inhibitors, omeprazole, lansoprazole, and pantoprazole, as well as any potential influence on CYP1A2 activity (measured by means of rate of caffeine metabolism) of these compounds at single dose and repeated dose administration.


METHODS
Fourteen healthy males, classified as 12 extensive metabolizers (EMs) and two poor metabolizers (PMs) according to the urinary S/R mephenytoin ratio, completed this open, randomized, three-way cross-over study. In each of the three 7-day treatment periods either omeprazole (20 mg), lansoprazole (30 mg) or pantoprazole (40 mg) in therapeutically recommended doses was administered once daily, and the pharmacokinetics of the proton pump inhibitors as well as the rate of caffeine metabolism was measured on days 1 and 7.


RESULTS
In the EMs there was an increase in AUC from day 1 to day 7 for omeprazole. In the PMs the AUC of both omeprazole and lansoprazole was unchanged during repeated dosing, while for pantoprazole there was a tendency to a slight decrease. The AUC at steady state was for all three proton pump inhibitors 5 fold higher in PMs compared with EMs, indicating that the same proportion of the dose, irrespective of compound, is metabolized by CYP2C19. No induction of CYP1A2 was evident for any of the compounds in either EMs or PMs.


CONCLUSIONS
The approximately 5 fold difference in AUC between EMs and PMs indicates that approximately 80% of the dose for all three proton pump inhibitors is metabolized by the polymorphically expressed CYP2C19. None of the three proton pump inhibitors, administered in therapeutically recommended doses, is an inducer of CYP1A2--neither in PMs nor in EMs.
Andersson
T
T
Clinical Research & Development, Astra Hässle AB, Mölndal, Sweden.
Holmberg
J
J
Röhss
K
K
Walan
A
A
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D019540:Area Under Curve; D001562:Benzimidazoles / Q000493:pharmacokinetics* / Q000494:pharmacology; D001944:Breath Tests; D002110:Caffeine / Q000378:metabolism* / Q000652:urine; D006801:Humans; D064747:Lansoprazole; D008297:Male; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000494:pharmacology; D000077402:Pantoprazole; D054328:Proton Pump Inhibitors; D013454:Sulfoxides / Q000493:pharmacokinetics* / Q000494:pharmacology
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D001562:Benzimidazoles; D054328:Proton Pump Inhibitors; D013454:Sulfoxides; D064747:Lansoprazole; D002110:Caffeine; D000077402:Pantoprazole; D009853:Omeprazole