Study on long-term toxicity of ketoconazle in dogs / 中国药理学通报

ABSTRACT

Ketoconazole(KET) is a new imi-dazole derivative with broad antimycotic spectrum. In order to verify the clinical toxic and side effect and its properties in animals, we made a long-term toxicity test for 30 days. Dosages of 70, 35 and 17. 5 mg?kg-1?d-1(e-quivalent to 21, 10. 5 and 5. 2 times of the clinical dosage) were given ig to dogs. The salivation , vomiting, anorexia, decrease in heart rate and loss of weight occurred in the large dosage group. Half of the dogs died from toxicosis within ig 15 days. Laboratory examination showed that the activities of ALT, LDH and ALP, the content of T-BIL, BUN in serum in-creased in this group. Pathological examination revealed that there were some pathological changes in the liver, kidneys, adrenal glands and sex gland in the group. There were no significant changes in other dosage groups compared with the normal control group. After withdrawal of KET, all toxic symptoms disappeared and the abnormal indexes were restored. The results indicated that toxic target organs of KET were liver, kidney, adrenal gland and sex glands. The safe dosage for dogs was about 17. 5 mg?kg-1?d-1.