Comparative Single‐Dose Kinetics and Effects of Four Sulfonylureas in Healthy Volunteers

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Abstract
The single-dose kinetics and effects of tolbutamide (500 mg), chlorpropamide (250 mg), glibenclamide (5 mg) and glipizide (5 mg) were compared in 7 healthy male volunteers by measurements of serum concentrations of the drugs and of plasma insulin and blood glucose. The drugs were administered both on an empty stomach and together with a standardized breakfast. The concentrations of tolbutamide and chlorpropamide were measured by gas chromatography, those of glipizide with high-pressure liquid chromatography, those of glibenclamide and insulin by radioimmunoassay and those of glucose by the hexokinase method. Glipizide and glibenclamide were more potent inducers of insulin release and blood glucose reduction than tolbutamide and chlorpropamide. As the concentrations of the former 2 drugs were in the range of nmol/l and those of the latter 2 in the .mu.mol/l range, the intrinsic activity of the 2 second-generation sulfonylureas apparently is at least 1000 times greater than that of the 2 1st-generation drugs. Glipizide seemed to be a more potent and more rapid insulin releaser than glibenclamide, but this may be secondary to biopharmaceutic differences between the 2 preparations. The bioavailability of glipizide was apparently greater than that of glibenclamide. Both glibenclamide (t1/2 [half-time] = 1.8 h) and glipizide (t1/2 = 4.3 h) showed much shorter elimination t1/2 than tolbutamide (7 h) and chlorpropamide (34 h). It seems probable that these t1/2 are not fully informative as to the duration of action of the drugs.