Ruenitz P C, Bagley J R
Drug Metab Dispos. 1985 Sep-Oct;13(5):582-6.
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.
三芳基乙烯类抗雌激素药物氯米芬（CLO）和他莫昔芬（TAM）在体外均已被证明可转化为“活性”代谢产物，这些代谢产物可能有助于其抗雌激素作用。我们研究了CLO和TAM在未成熟雌性大鼠体内的处置情况，大多数关于抗雌激素作用的生化研究都是以这种动物模型进行的。腹腔注射后，两种药物主要通过粪便排出，在24小时内，CLO的排出效率（57%）是TAM（19%）的三倍。CLO的大部分剂量以原形排出；TAM的大部分剂量以代谢产物形式排出，尤其是4-羟基-TAM。腹腔注射24小时后，TAM在肝脏和子宫组织中伴有一系列代谢产物。相比之下，注射CLO后，在这些组织中从肝脏微粒体匀浆存在时产生的代谢产物的回收率可忽略不计。相反，在这些组织中，一种成分不明的极性物质与未改变的CLO相伴。这些结果再次证实了TAM的作用部分归因于其代谢产物这一事实，并表明，相比之下，CLO的作用主要归因于未改变的药物。
