Metabolism profiles and excretion of ¹⁴C-aminoglutethimide in several animal species and man

Abstract

1. Following administration of a single oral dose of ¹⁴C-aminoglutethimide to rats, guinea-pigs, rabbits and man, >89% of the dose was excreted in urine and faeces within 72 h; dogs eliminated only 51% in this time.

2. Extensive metabolism occurred in all species, with N-acetylaminoglutethimide being the major metabolite except for dog and man. In the latter two species unchanged drug was the main product excreted.

3. A metabolite, 3-(4-acetamidophenyl)-3-(2-carboxamidoethyl)tetrahydrofuran-2-one, not previously found in human urine, was identified.

4. Chronic administration of aminoglutethimide to rats produced no detectable change in the excretory or metabolite patterns of the drug. However chronic administration of phenobarbitone decreased the urinary excretion of ¹⁴C over a 72 h period.

5. Residual (72h) tissue levels of ¹⁴C were <1 μg equivalent of ¹⁴C-amino-glutethimide/g tissue in the rat, guinea-pig and rabbit. Dog tissues retained a considerable quantity of ¹⁴C at this time.