Sex- and species-related nephropathy of 6-(1-aminocyclohexanecarboxamido)penicillanic acid (cyclacillin) and its relationship to the metabolic disposition of the drug
| Autor: | Hans W. Ruelius, Frank W. Janssen, H.P.K. Agersborg, Emily M. Young, Walter E. Tucker |
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| Rok vydání: | 1974 |
| Předmět: |
Male
medicine.medical_specialty Necrosis Cyclacillin Biology Toxicology Nephropathy Nephrotoxicity Muscle hypertrophy Excretion Dogs Sex Factors Species Specificity Internal medicine medicine Animals Pharmacology Hyperplasia medicine.disease Macaca mulatta Rats Endocrinology Toxicity Female Kidney Diseases medicine.symptom |
| Zdroj: | Toxicology and applied pharmacology. 29(1) |
| ISSN: | 0041-008X |
| Popis: | In COBS-CD rats treated with cyclacillin for 4 weeks there were no drug-related histologic changes, but after 26 weeks of treatment a chronic proliferative and degenerative nephropathy was observed in males but not in females. Morphologic features of the nephropathy included renal enlargement, cystic tubular dilatation, tubular epithelial degeneration, hypertrophy and hyperplasia, and chronic interstitial inflammation and necrosis. Neither rhesus monkeys nor beagle dogs developed the renal lesions after comparable treatment. Nephrotoxic effects were not found in humans given therapeutic doses (2000 mg/day) for 30 days. In correlation with the nephrotoxic effect noted in the male rat, one of the metabolites of cyclacillin, 2-aminocyclohexanecarboxylic acid (ACHC), accumulated to a greater extent in the male than in the female. This sex difference was attributed to a lower rate of excretion of the metabolite in the male. The accumulation of ACHC is thought to be partly responsible for the nephrotoxicity, but the intact drug probably also contributes to the toxicity. The excretion rate of cyclacillin itself was also sex-related in the rat at low but not at high dose. ACHC also accumulates to some extent in dogs of both sexes chronically treated with cyclacillin, but not in similarly treated rhesus monkeys or in humans given 2000 mg/day for 30 days. |
| Databáze: | OpenAIRE |
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