两性霉素B甲酯与两性霉素B在小鼠、大鼠和犬中的比较毒理学研究。
Comparative toxicological studies of amphotericin B methyl ester and amphotericin B in mice, rats, and dogs.
作者信息
Keim G R, Sibley P L, Yoon Y H, Kulesza J S, Zaidi I H, Miller M M, Poutsiaka J W
出版信息
Antimicrob Agents Chemother. 1976 Oct;10(4):687-90. doi: 10.1128/AAC.10.4.687.
In acute and subacute toxicological studies, amphotericin B methyl ester was shown to be much less toxic than the parent antibiotic. As a single intravenous dose in mice, the methyl ester was approximately 20 times less toxic than amphotericin B. Also, the acute toxicity of the methyl ester in mice was not enhanced by the presence of chemically induced hepatic or renal damage or by the concurrent administration of amphotericin B or flucytosine. In a 1-month intraperitoneal study in rats, the methyl ester was about one-fourth as nephrotoxic as amphotericin B. In a 1-month intravenous study in dogs, the methyl ester was about one-eighth as nephrotoxic and one-fourth to one-half as hepatotoxic as the parent compound. In addition, the methyl ester, unlike amphotericin B, produced minimal renal effects, which did not increase in severity with increasing dosage. Based on the results of these studies, it is concluded that amphotericin B methyl ester has the potential for an improved therapeutic ratio in the treatment of systemic mycoses.
在急性和亚急性毒理学研究中，两性霉素B甲酯的毒性比其母体抗生素低得多。作为小鼠的单次静脉注射剂量，甲酯的毒性比两性霉素B低约20倍。此外，化学诱导的肝损伤或肾损伤的存在，或同时给予两性霉素B或氟胞嘧啶，均未增强甲酯在小鼠中的急性毒性。在大鼠的1个月腹腔内研究中，甲酯的肾毒性约为两性霉素B的四分之一。在犬的1个月静脉内研究中，甲酯的肾毒性约为母体化合物的八分之一，肝毒性为四分之一至二分之一。此外，与两性霉素B不同，甲酯产生的肾脏影响极小，且严重程度不会随剂量增加而增加。基于这些研究结果，得出结论：两性霉素B甲酯在治疗全身性真菌病方面有可能提高治疗指数。
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