The Metabolism of Tamoxifen (I.C.I. 46,474) Part I : In Laboratory Animals

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Abstract
1. The metabolism and excretion of a non-steroidal oestrogen antagonist, tamoxifen (I.C.I. 46,474) [trans-1-(p-β-dimethylaminoethoxyphenyl)-1,2-diphenylbut-1-ene], has been studied in rat, mouse, rhesus monkey and dog using the 14C-labelled compound. 2. In all species the compound was well absorbed and extensively metabolized after oral administration. The 14C was slowly eliminated, largely in the faeces. No loss of 14C as carbon dioxide could be detected in expired air from small animals. 3. In most of the species levels in the blood were low and showed two maxima following oral dosing. Enterohepatic circulation was demonstrated in rat and dog. 4. Metabolic patterns were qualitatively similar in all the species examined. Metabolites were isolated from faecal extracts and bile. Most of the 14C-labelled material was present as glucuronides and other conjugates. Hydroxylation was a significant metabolic pathway in all species. 5. A novel metabolite formed by deamination of the side chain, hydroxylation of an aromatic ring and oxidation of the ethyl group was present in rat bile.