Effects of Diabetes on Disposition and Hepatic Handling of Cefmetazole in Rats

Abstract

1. The effects of streptozotocin-induced diabetes on disposition and hepatic handling of cefmetazole, a broad-spectrum cephalosporin, were investigated in rats. 2. Male Wistar rats were pretreated with streptozotocin (60 mg/kg, i.p.) to induce uncontrolled diabetes. Fourteen days later bile flow was significantly reduced (12%) and bile acid secretion was significantly enhanced (87%) when compared with control animals. 3. Following intravenous injection of cefmetazole at a dose of 200 mumol/kg, maximal and cumulative biliary excretion of the antibiotic were significantly impaired in streptozotocin-treated animals (27 and 22%, respectively). 4. Cefmetazole excretion into bile was accompanied by marked choleresis. The magnitude of bile flow increase was larger in control animals. 5. Total systemic clearance of the antibiotic was reduced (36%) and mean half-life for the fast and slow phases of disposition increased (136 and 48%, respectively) in diabetic rats. 6. These changes were probably due to the diabetic condition of the animals because insulin treatment resulted in almost complete correction.