Interindividual variation in the absorption of glibenclamide in man

Abstract

To investigate the interindividual variation in the absorption of sulphonylureas and its relation to unexpected hypoglycaemia during therapy with these drugs, serum concentration profile of glibenclamide, as well as plasma glucose and insulin response after an oral intake of glibenclamide were studied in 17 patients with non-insulin-dependent diabetes mellitus. In 12 patients glibenclamide was rapidly absorbed, reaching a peak concentration of 138.0 \ m=+-\ 15.8 ng/ml (mean \ m=+-\ SEM) at about 2 h. However, in 5 patients the absorption of glibenclamide was delayed and reached a serum peak of 134.1 \m=+-\29.5 ng/ml at later than 4 h. This delayed absorption was reproducible. There were no significant differences in age, duration of diabetes, per cent of ideal body weight, fasting plasma glucose or HbA 1C between the rapid absorption group and the delayed group. However, autonomic nerve function, assessed by coefficient of variation of R-R intervals, was significantly impaired in the latter group in comparison with the former. Plasma glucose and insulin response to glibenclamide was also delayed in the delayed absorption group.

The effects of magnesium hydroxide on the absorption and efficacy of two glibenclamide preparations.

“…However, the increased rate and extent of glibenclamide absorption, especially from the non-micronised formulation, appear to be of potential clinical importance. In diabetic patients, drug absorption may be delayed owing to autonomic neuropathy (Ikegami et al, 1986). Therefore, there is a possibility that magnesium hydroxide could have a more pronounced effect in diabetic patients with gastroparesis, even affecting the absorption of micronised glibenclamide.…”

“…Certain diabetic patients appear to have delayed absorption of sulphonylureas, as shown for both glipizide and glibenclamide (Ikegami et al, 1986;Kradjan et al, 1989). It has been suggested that this may lead to unexpected hypoglycaemia because of the time discrepancy between drug effect and food intake (Ikegami et al, 1986).…”

“…It has been suggested that this may lead to unexpected hypoglycaemia because of the time discrepancy between drug effect and food intake (Ikegami et al, 1986). Glibenclamide seems to be more likely to provoke long-lasting and sometimes even fatal hypoglycaemia than other sulphonylureas (Ferner & Neil, 1989).…”

“…Different glibenclamide preparations can, however, have quite different rates and extents of absorption, and, consequently, their effects on blood glucose are not identical (Haupt et al, 1984;Karttunen et al, 1985). The non-micronised preparations are slowly and incompletely absorbed, and display large interindividual variation in their absorption (Ikegami et al, 1986;Neugebauer et al, 1985). Micronised formulations with a higher surface area have therefore been developed to improve the pharmacokinetic properties of glibenclamide.…”

“…Micronised formulations with a higher surface area have therefore been developed to improve the pharmacokinetic properties of glibenclamide. Autonomic neuropathy, resulting in delayed gastric emptying, may cause additional variability in the absorption of glibenclamide in diabetic patients (Ikegami et al, 1986).…”