Metabolic and pathologic investigation of 1-aminocyclohexanecarboxylic acid (ACHC), a metabolite of 6-(1-aminocyclohexanecarboxamido)-penicillanic acid (cyclacillin)
| Autor: | Hans W. Ruelius, Sandra K. Kirkman, Emily M. Young, Frank W. Janssen, H.P.K. Agersborg, Walter E. Tucker |
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| Rok vydání: | 1974 |
| Předmět: |
Male
medicine.medical_specialty Cyclohexanecarboxylic Acids Metabolite Cyclacillin Penicillanic Acid Pharmacology Toxicology Nephrotoxicity chemistry.chemical_compound Urinary excretion Metabolic breakdown Dogs Sex Factors Internal medicine medicine Animals Amino Acids Rats Inbred Strains Rats Endocrinology chemistry Renal physiology Plasma concentration Female Kidney Diseases |
| Zdroj: | Toxicology and applied pharmacology. 29(1) |
| ISSN: | 0041-008X |
| Popis: | A nephrotoxic effect was noted in male but not in female COBS-CD rats chronically treated with 1-aminocyclohexanecarboxylic acid (ACHC), a metabolite of 6-(1-aminocyclohexanecarboxamido)penicillanic acid (cyclacillin). The renal changes were qualitatively similar to, but less severe than, those observed with the parent compound. In correlation with the histopathologic findings, the rate of urinary excretion (the primary route of elimination for ACHC) was lower and the accumulation of ACHC in plasma and tissues was higher in males than in females. Following termination of chronic dosing the concentrations in the plasma of females decreased in 2 phases, with a t 1 2 of 14 hr for the first and 31 hr for the second. In similarly treated males, the respective phases were 4 days and 8.5 days. There was no evidence of metabolic breakdown of ACHC in the rat. In the dog there was little sex difference in disposition of ACHC, and both renal excretion and decline in plasma concentrations were between the values for the male and female rat. |
| Databáze: | OpenAIRE |
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