TOXICITY STUDY ON AZTHREONAM (3):35-DAY SUBACUTE TOXICITY BY SUBCUTANEOUS ROUTE IN RATS

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A 35-day subacute toxicity study on Azthreonam (AZT), a newly developed monobactam antibiotic, was conducted by subcutaneous injection in Sprague-Dawley rats. The following dose-related changes in clinical laboratory examinations were detected in the animals received AZT: slightly increased water intake (150 mg/kg or more), decreased RBC count (300 mg/kg or more), subcutaneous edema and hemorrhage at the injection site, lower levels of Al-P, GPT, glucose, total protein, albumin and Ca (600 mg/kg or more). Organ weight analysis showed increased weights of liver, caecum, carcass (300 mg/kg or more), kidney (600 mg/kg or more) and spleen (1, 200 mg/kg or more). Histopathologic examination revealed vacuolation in the renal proximal tubular epithelial cells, subcutaneous inflammation at the injection site (600 mg/kg or more) splenic extramedullary hyperhematopoiesis and hypertrophy of hepatocyte (1, 200 mg/kg or more). Other than mentioned above, depressed growth, decreased thymus weight, hyperplasia of erythropoiesis in the bone marrow and each of two deaths out of ten of both sexes, which showed vacuolation of hepatocyte and renal proximal tubular epithelium, and necrosis of renal proximal tubule (pars recta), were observed in the animals received 2, 400 mg/kg of AZT. The above dose-related changes except dead animals were returned to normal after 35 days cessation of treatment.
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