LACK OF PANTOPRAZOLE DRUG-INTERACTIONS IN MAN

This review summarizes the results of pharmacokinetic and pharmacodyna mic drug interaction studies in man with pantoprazole, a new, selectiv e proton pump inhibitor. Different mechanisms have to be considered as causes for potential drug-drug interactions. Proton pump inhibitors ( PPIs) in general may alter the absorption of drugs by increasing the i ntragastric pH. Due to the presence of an imidazole ring, the PPIs of the class of substituted benzimidazole sulfoxides may interfere with t he metabolism of other drugs by altering the activity of drug metaboli zing enzymes of the cytochrome P450 system, via either induction or in hibition. With the increasing use of PPIs, their interaction potential gains therapeutic importance as was the case with the first and secon d generation of H-2-blockers (cimetidine and ranitidine, respectively) . The enhanced selectivity of pantoprazole to the gastric H+/K+-ATPase characterizes the new PPI generation. In comparison to omeprazole and lansoprazole, pantoprazole showed a much lower affinity to cytochrome P450 in vitro and a markedly lower potency in the in vivo rat model f or interaction with diazepam In contrast to omeprazole, pantoprazole d oes not interact with the cytochrome P450 system in man. In the drug i nteraction studies conducted so far, pantoprazole did not affect the p harmacokinetics or pharmacodynamics of antipyrine, diazepam, digoxin, a hormonal contraceptive, nifedipine, phenytoin, theophylline and warf arin in man. Also pantoprazole neither induced the drug metabolism of antipyrine nor increased urinary excretion of the induction markers D- glucaric acid and 6 beta-hydroxycortisol. Vice versa, the investigated drugs had no relevant influence on the pharmacokinetics of pantoprazo le.