Ie. Waltersack et al., LACK OF PHARMACOKINETIC AND PHARMACODYNAMIC INTERACTION BETWEEN PANTOPRAZOLE AND GLIBENCLAMIDE IN HUMANS, Clinical drug investigation, 15(3), 1998, pp. 253-260
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.