Lack of drug interaction between omeprazole, lansoprazole, pantoprazole and theophylline

Aims Theophylline is a model substrate of cytochrome P4501A2. The ability o f the proton pump inhibitors (PPI) omeprazole, lansoprazole and pantoprazol e 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 m etabolisers of cytochrome P4502C19 and Helicobacter pylori negative) partic ipated in a randomized, double-blind, four-period, placebo-controlled cross over 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 coadminist ered from day 8-10. Pharmacokinetics of theophylline as well as of all thre e 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 conce ntrations and peak-trough fluctuations of theophylline were not altered by PPI pretreatment and met the required limits for bioequivalence. Point esti mates (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.