EFFECTS OF DIABETES ON DISPOSITION AND HEPATIC HANDLING OF CEFMETAZOLE IN RATS

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