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Wiley InterScience | ||||||
  British Journal of Clinical PharmacologyVolume 48 Issue 3, Pages 438 - 444 Published Online: 24 Dec 2001 Journal compilation © 2010 The British Pharmacological Society The Journal of The British Pharmacological Society
Abstract | References | Full Text: HTML, PDF (Size: 218K) | Related Articles | Citation Tracking  Lack of drug interaction between omeprazole, lansoprazole, pantoprazole and theophylline Copyright 1999 Blackwell Science Ltd KEYWORDS cytochrome P4501A2 • drug interaction • proton pump inhibitors • theophylline ABSTRACTAims 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. | 
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