LACK OF PHARMACOKINETIC AND PHARMACODYNAMIC INTERACTION BETWEEN PANTOPRAZOLE AND GLIBENCLAMIDE IN HUMANS

The new H+/K+-ATPase inhibitor pantoprazole potently inhibits gastric acid secretion and is highly effective in the treatment of peptic ulce ration. Pantoprazole is metabolised in the liver by CYP2C19 and CYP3A4 . The sulfonylurea glibenclamide, widely used for treatment of type 2 diabetes mellitus, is metabolised mainly in the liver by CYP3A. As sub stituted benzimidazoles may potentially interact with the cytochrome P 450 system, the influence of pantoprazole on the pharmacokinetics and pharmacodynamics of glibenclamide was investigated. 18 healthy male vo lunteers completed a randomised crossover study according to protocol. They received 40mg pantoprazole or placebo for 5 days each, and conco mitantly 3.5mg glibenclamide (micronised preparation) on the 5th day. Additionally, 40mg pantoprazole alone was administered on a separate d ay. Glibenclamide, pantoprazole, glucose and insulin serum concentrati ons were measured. The lack of a pharmacokinetic interaction was handl ed as an equivalence problem. Equivalence was demonstrated for the pri mary characteristic area under the concentration-time curve (AUG) of g libenclamide with and without pantoprazole. Although the upper 90% con fidence limit of 1.26 for maximum serum concentration (C-max) of glibe nclamide was marginally outside the equivalence range of 0.80 to 1.25, it can be concluded that pantoprazole does not influence the pharmaco kinetics of glibenclamide in a clinically relevant way. Conversely, gl ibenclamide did not affect the pharmacokinetics of pantoprazole. The p harmacodynamic profiles of glucose and insulin on day 5 were equivalen t with and without pantoprazole. Apart from the glucose-lowering actio n of glibenclamide, no drug-related adverse events occurred. In conclu sion, no dose adjustment is required during concomitant treatment with a micronised preparation of glibenclamide and pantoprazole.