Identification and distribution in the rat of acidic metabolites of tamoxifen.

Chromatographic analysis of acidic fractions of urinary radioactivity from immature female rats which had received the triarylethylene antiestrogen tamoxifen (TAM), labeled with 14C, resulted in the identification of two new metabolites. These were tamoxifen acid (TA), in which the side chain of TAM was changed to an oxyacetic acid moiety, and 4-hydroxytamoxifen acid (4-HTA), which had a similarly altered side chain plus a phenolic hydroxy group in its structure. In contrast to other TAM metabolites and other arylacetic acids, neither TA nor 4-HTA were eliminated as glucuronic acid or glycine conjugates in urine. Only small amounts of acidic radioactivity were found in liver tissue 24 and 48 hr after dosing, and none was detected in uterine tissue. However, TA plus 4-HTA accounted for 2.8% and 2.9% of the administered dose eliminated within 24 hr in urine and feces, respectively. These results suggest that TA and 4-HTA are important final products of TAM metabolism and that these, unlike other hydroxylated and/or dealkylated metabolites of this drug, may not contribute to the antiuterotrophic effects of TAM.