1978 Volume 98 Issue 9 Pages 1208-1214
Absorption, excretion, and metabolism of Glybuzole (2-benzenesulfonamido-5-tert-butyl-1-thia-3, 4-diazole) were studied in normal rats, and rats pretreated with phenobarbital, SKF 525A, or carbon tetrachloride. Plasma half-life of 14C-Glybuzole after its oral administration was affected by the pretreatment ; phenobarbital, 4.5 hr ; SKF 525A, 28 hr ; carbon tetrachloride, 34 hr ; and nontreated, 7 hr. Urinary, fecal, and biliary excretion of Glybuzole was also affected by these pretreatments. Glybuzole was excreted in urine 2.5 times higher in carbon tetrachloride-pretreated rats than in normal rats. Biliary excretion of Glybuzole in normal rats reached 91.1% of administered radioactivity within 48 hr, indicating the presence of enterohepatic circulation. Major urinary metabolites were the unchanged drug, a metabolite (I) oxidized at the tert-butyl side-chain, a novel metabolite (II) oxidized at the position para to the phenyl group of Glybuzole, and their O- or N-glucuronides. Unchanged drug was major and metabolites I and II were minor components. In bile, glucuronides, mainly N-glucuronide of Glybuzole, were major metabolites. Carbon tetrachloride pretreatment suppressed the excretion of N-glucuronide. The plasma metabolites (I and II) had no antidiabetic activity in rabbits.
