D. Smith, T. J. Vecchio, A. A. Forist
Mar 1, 1965
Citations
0
Influential Citations
33
Citations
Quality indicators
Journal
Metabolism: clinical and experimental
Abstract
Abstract The p -acetylbenzenesulfonylureas, 1-( p -acetylbenzenesulfonyl)-3-(hexahydro-1H-azepin-1-yl)-urea (U-18536) and 1-( p -acetylbenzenesulfonyl)-3-cyclohexylurea (acetohexamide), are rapidly absorbed and rapidly metabolized in man by reduction to their corresponding p -α-hydroxyethyl derivatives. After oral administration of 500 mg. of each drug to human subjects, serum concentrations of the drugs and their p -α-hydroxyethyl metabolites were determined at intervals for 15 hours. The average biological half-life of U-18536 in 8 nondiabetic male subjects was found to be 2.1 ± 0.2 (S.E.M.) hours, whereas the average half-life of its metabolite was found to be 3.0 ± 0.2 hours. The average biological half-lives of acetohexamide and its p -α-hydroxyethyl metabolite were found to be 1.3 ± 0.1 hours and 4.6 ± 0.9 hours, respectively. For both U-18536 and acetohexamide, the aparent half-life of disappearance of total sulfonylureas (drug plus metabolite) from the serum is essentially equal to that of their metabolites. Duration of hypoglycemic effect correlates best with total sulfonylureas in the serum, which is in agreement with the observation that the p -α-hydroxyethyl metabolites have hypoglycemic activity. Based on the biological half-lives of total sulfonylureas, intact drug or metabolite, neither U-18536 nor acetohexamide has a duration advantage over tolbutamide.