Article date: June 1987
By: RT Kubacka, EJ Antal, RP Juhl, in Volume 23, Issue 6, pages 743-751
The potential interactions between H2‐receptor antagonists, cimetidine and ranitidine, and glibenclamide were studied in 15 non‐smoking male volunteers. The study consisted of six treatment phases. Treatment A (3 h oral glucose tolerance test) consisted of 75 g dextrose in 300 ml carbonated water. Treatment B consisted of one 5 mg tablet of glibenclamide in addition to a glucose tolerance test. Treatment C, cimetidine 300 mg orally four times daily for 4 days and Treatment D, ranitidine 150 mg orally twice daily for 4 days were administered in a randomized, crossover fashion. On day 3 of Treatments C and D, subjects received an oral glucose tolerance test. On day 4 of Treatments C and D, subjects received 5 mg of glibenclamide in addition to cimetidine (Treatment E) or ranitidine (Treatment F) and an oral glucose tolerance test. Compared with the control treatment, cimetidine increased the glibenclamide AUC (973 vs 710 ng ml‐1 h), but during ranitidine dosing glibenclamide AUC (726 ng ml‐1 h) was not significantly different from the control. Apparent oral glibenclamide clearance decreased from 8.25 l h‐1 under the control treatment to 6.0 l h‐1 following cimetidine but was unchanged during ranitidine (7.97 l h‐1). Plasma glucose concentrations were unexpectedly higher when glibenclamide was administered with cimetidine or ranitidine (glucose AUC 237 mg dl‐1 h, 228 mg dl‐1 h) when compared with glibenclamide administered alone (195 mg dl‐1 h, P less than 0.0001). Plasma insulin concentrations were significantly elevated when H2‐receptor antagonists and glibenclamide were administered concurrently.(ABSTRACT TRUNCATED AT 250 WORDS)
DOI: 10.1111/j.1365-2125.1987.tb03110.x
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