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EFFECTS OF DIABETES ON DISPOSITION AND HEPATIC HANDLING OF CEFMETAZOLE IN RATS
Author(s) -
Barrientos C.,
González P.,
Tuñón M. J.,
Culebras J. M.,
GonzálezGallego J.
Publication year - 1993
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1993.tb01716.x
Subject(s) - cefmetazole , disposition , diabetes mellitus , medicine , pharmacology , endocrinology , chemistry , psychology , biochemistry , cephalosporin , social psychology , antibiotics
SUMMARY 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 μmol/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 cofrection.