Tissue distribution and elimination of14C-aminoglutethimide in the mouse

Abstract

Following oral administration of 14C-aminoglutethimide (Orimeten), male mice excreted 75% and female mice 59% of the administered dose during 24 h. After 72 h, elimination was essentially complete in male mice, whilst recovery from female mice was 74%. As assessed by quantitative assay and whole-body autoradiography, a wide distribution of radioactivity was found with high concentrations of radioactivity occurring only in the bile, gastro-intestinal tract and liver at early times. Residual (72 h) tissue levels of radioactivity were less than 1 microgram equiv. of 14C-aminoglutethimide/g tissue. Metabolite profiles in urine, tissues and faeces showed extensive metabolism of the drug in a pattern similar to that found in the rat.

Pharmacokinetics of the S- and R-enantiomers of aminoglutethimide in saliva of breast cancer patients: Correlations with plasma

“…The values obtained in the present work are within the range previously reported for racemic AG by Adam et al 14 and Lonning et al 15 A value of 70 to 80 L is consistent with an even pattern of distribution for a drug of average lipophilicity (equivalent to that of ethanol) that is not highly bound to plasma protein and tissue macromolecules. This interpretation for AG in man is in agreement with AG tissue distribution data in animals 16 and plasma binding (20%-30%) in man. 17,18 The 1.6-fold difference in mean total clearance of AG (S > R) was significant (p ≤ 0.02).…”