Uniform elimination pattern for glibenclamide in healthy Caucasian males

It has been shown, that the elimination rate of intravenously administered tolbutamide shows considerable interindividual variation, due to strong genetic influence. These pharmacogenetic differences in the metabolic clearance rate of tolbutamide may result in drug failure in fast-eliminators, and it may cause an increased incidence of side effects in slow-eliminators. It is not known whether different "pharmacogenetics" exist for other sulfonylurea drugs. Therefore, we have injected glibenclamide (0.02 mg/kg body weight) intravenously in 52 male, normal weight, healthy volunteers. Serum glibenclamide levels were followed for up to 24 h. The terminal phase half-life of glibenclamide was 2.46 +/- 0.67 h (mean +/- SD), total drug clearance was 48.7 +/- 11.0 ml.min-1 and the slow disposition phase rate constant was 0.30 +/- 0.08 h-1. From the individual data of each subject frequency histograms were developed for these and other kinetic parameters and tested with a Kolmogoroff-Smirnoff-test for unimodal normal distribution. There was no significant (p greater than 0.05) deviation from the unimodal normal distribution for these parameters. In contrast to the pharmacogenetics of tolbutamide metabolism the present data indicate that glibenclamide follows an uniform elimination pattern in healthy caucasian males.