Summary
Eight-week-old Wistar female rats were treated intramuscularly with 300, 1,000 and 3,000 mg/kg/day of cefotiam for five days. The nephrotoxicity of cefotiam was determined on the basis of the number of tubular epithelial cells excreted, the malate dehydrogenase activity in the urine and the histological examination of the kidneys. Cephalothin (3,000 mg/kg/day) was used as a reference compound. There were slight increases in the number of tubular epithelial cells excreted and in the malate dehydrogenase activity in the urine of some animals receiving 3,000 mg/kg/day of cefotiam or cephalothin. All of these changes disappeared within a few days after the dosing period. The histological examination of the kidneys at the end of both the dosing (5 days) and the recovery (7 days) periods revealed no pathological changes indicating nephrotoxicity. It was concluded that the nephrotoxicity of cefotiam was comparable to that of cephalothin; the urinary changes in animals receiving the highest dose were considered to be an early sign of nephrotoxicity. The maximum non-toxic dose of cefotiam was 1,000 mg/kg/day under the present experimental conditions.
Zusammenfassung
Acht Wochen alte, weibliche Wistarratten erhielten fünf Tage lang 300, 1000 oder 3000 mg Cefotiam pro kg/Tag i. m. Die Nephrotoxizität wurde an der Zahl der ausgeschiedenen Tubulusepithelien, der Malat-Dehydrogenase-Aktivität im Urin gemessen und durch histologische Untersuchung der Nieren geprüft. Cephalotin (3000 mg/kg/Tag) wurde als Referenzsubstanz verwendet. Bei einigen der Tiere, die Cefotiam oder Cephalotin in einer Dosis von 3000 mg/kg/Tag erhielten, war die Zahl der ausgeschiedenen Tubulusepithelien und die Malat-Dehydrogenase-Aktivität im Urin leicht erhöht. Diese Veränderungen verschwanden wenige Tage nach der Dosierungsphase. Am Ende sowohl der Dosierungsphase (5 Tage) als auch der Erholungsphase (7 Tage) waren histologisch keine pathologischen Veränderungen im Sinne einer Nephrotoxizität festzustellen. Die Nephrotoxizität von Cefotiam und Cephalotin war vergleichbar; Veränderungen der Urinbefunde bei den höchsten Dosen wurden als Frühzeichen der Nephrotoxizität beurteilt. Unter den vorliegenden experimentellen Bedingungen war die maximale untoxische Dosis von Cefotiam 1000 mg/kg/Tag.
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Nakai, Y., Chiba, S., Suhara, I. et al. Nephrotoxicity of cefotiam in rats. Infection 11, 283–285 (1983). https://doi.org/10.1007/BF01641264
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DOI: https://doi.org/10.1007/BF01641264