Lack of drug interaction between omeprazole, lansoprazole, pantoprazole and theophylline.
OBJECTIVE
Theophylline is a model substrate of cytochrome P4501A2. The ability of the proton pump inhibitors (PPI) omeprazole, lansoprazole and pantoprazole to induce cytochrome P4501A2 has not yet been unequivocally resolved. The aim of this comprehensive study was to compare directly the effect of the three PPI on the absorption and disposition of theophylline.


METHODS
Twenty healthy, nonsmoking, male and female volunteers (extensive metabolisers of cytochrome P4502C19 and Helicobacter pylori negative) participated in a randomized, double-blind, four-period, placebo-controlled crossover study. In each of the four periods they received either omeprazole (40 mg), lansoprazole (60 mg), pantoprazole (80 mg) or placebo once daily for 10 days. Sustained release theophylline (350 mg twice daily) was coadministered from day 8-10. Pharmacokinetics of theophylline as well as of all three PPI were determined at steady-state (day 10).


RESULTS
In all periods, point estimates and 90% confidence intervals of the area under the concentration-time curves (AUC), maximum steady-state concentrations and peak-trough fluctuations of theophylline were not altered by PPI pretreatment and met the required limits for bioequivalence. Point estimates (90% confidence intervals) of the AUC ratios of theophylline plus PPI to theophylline alone were 0.92 (0.87-0.97), 0.90 (0.85-0.95) and 1.00 (0.95-1.06) for omeprazole, lansoprazole and pantoprazole, respectively.


CONCLUSIONS
Concomitant intake of omeprazole, lansoprazole or pantoprazole at high therapeutic doses does not affect the absorption and disposition of theophylline.
Dilger
K
K
Dr Margarete Fischer-Bosch-Institut für Klinische Pharmakologie, Stuttgart, Germany.
Zheng
Z
Z
Klotz
U
U
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000328:Adult; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D019540:Area Under Curve; D001562:Benzimidazoles / Q000494:pharmacology*; D001993:Bronchodilator Agents / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D006801:Humans; D064747:Lansoprazole; D008297:Male; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000077402:Pantoprazole; D054328:Proton Pump Inhibitors; D013454:Sulfoxides / Q000494:pharmacology*; D013806:Theophylline / Q000493:pharmacokinetics*
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D001562:Benzimidazoles; D001993:Bronchodilator Agents; D054328:Proton Pump Inhibitors; D013454:Sulfoxides; D064747:Lansoprazole; D013806:Theophylline; D000077402:Pantoprazole; D019388:Cytochrome P-450 CYP1A2; D009853:Omeprazole