Comparative fates of clomiphene and tamoxifen in the immature female rat.
The triarylethylene antiestrogens clomiphene (CLO) and tamoxifen (TAM) have each been shown to be converted in vitro to "active" metabolites which may contribute to their antiestrogenic effects. We have studied the disposition of CLO and TAM in the immature female rat, the animal model with which the majority of biochemical studies of the effects of antiestrogens have been conducted. Both drugs were eliminated mainly by the feces after ip administration, with CLO being eliminated three times as efficiently (57%) as TAM (19%) over 24 hr. Most of the dose of CLO was eliminated unchanged; most of the dose of TAM was eliminated as metabolites, especially 4-hydroxy-TAM. TAM was accompanied by an array of metabolites in liver and uterine tissues 24 hr after ip injection. In contrast, injection of CLO resulted in negligible recoveries from these tissues of metabolites demonstrated to be produced in the presence of liver microsomal homogenates. Instead, a polar material of unidentified composition accompanied unchanged CLO in these tissues. These results reconfirm the fact that the effects of TAM are due in part to its metabolites and suggest that, in contrast, the effects of CLO are due mainly to unchanged drug.
Ruenitz
P C
PC
Bagley
J R
JR
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D002996:Clomiphene / Q000378:metabolism*; D005260:Female; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013629:Tamoxifen / Q000378:metabolism*; D014316:Tritium
D013629:Tamoxifen; D014316:Tritium; D002996:Clomiphene