Effects of diabetes on disposition and hepatic handling of cefmetazole in rats.
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.
Barrientos
C
C
Department of Physiology, Pharmacology and Toxicology, University of León, Spain.
González
P
P
Tuñón
M J
MJ
Culebras
J M
JM
González-Gallego
J
J
D000818:Animals; D001646:Bile / Q000378:metabolism; D001647:Bile Acids and Salts / Q000378:metabolism; D001786:Blood Glucose / Q000032:analysis; D015311:Cefmetazole / Q000493:pharmacokinetics* / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D006207:Half-Life; D007328:Insulin / Q000494:pharmacology; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
D001647:Bile Acids and Salts; D001786:Blood Glucose; D007328:Insulin; D015311:Cefmetazole