LACK OF PANTOPRAZOLE DRUG-INTERACTIONS IN MAN - AN UPDATED REVIEW

This review summarizes the results of pharmacokinetic and pharmacodyna mic drug interaction studies in man with pantoprazole, a new, selectiv e proton pump inhibitor. Various mechanisms have to be considered as c auses for potential drug-drug interactions. Proton pump inhibitors (PP Is) in general may alter the absorption of drugs by increasing the int ragastric pH. Due to the presence of an imidazole ring, the PPIs of th e class of substituted benzimidazole sulfoxides may interfere with the metabolism of other drugs by altering the activity of drug metabolizi ng enzymes of the cytochrome P450 system, via either induction or inhi bition. With the increasing use of PPIs, their interaction potential g ains therapeutic importance as was the case with the first and second generation of H-2-blockers (cimetidine and ranitidine, respectively). The enhanced selectivity of pantoprazole to the gastric H+/K+-ATPase c haracterizes the new PPI generation. In contrast to omeprazole, pantop razole has a low potential to interact with the cytochrome P450 system in man. In the drug interaction studies conducted so far, substrates for all relevant cytochrome P450 families involved in the metabolism o f drugs in man were investigated. Pantoprazole did not affect the phar macokinetics or pharmacodynamics of antipyrine, caffeine, carbamazepin e, diazepam, diclofenac, digoxin, ethanol, glibenclamide, a hormonal c ontraceptive (combination of levonorgestrel and ethinylestradiol), met oprolol, nifedipine, phenprocoumon, phenytoin, theophylline and warfar in in man. Pantoprazole also neither induced the metabolism of antipyr ine or caffeine, nor increased urinary excretion of the induction mark ers D-glucaric acid and 6 beta-hydroxycortisol. Vice versa, the invest igated drugs had no relevant influence on the pharmacokinetics of pant oprazole.