Kirdani R Y, Mittelman A, Murphy G P, Sandberg A A
J Clin Endocrinol Metab. 1975 Aug;41(2):305-18. doi: 10.1210/jcem-41-2-305.
Estracyt, a conjugate of estradiol-17beta (E2) and a nitrogen mustard, is a compound which recently has been found to be of value in the treatment of cancer of the prostate. The present study concerned itself with the fate of labeled Estracyt administered 1) either as a mixture of 3H-Estracyt, labeled in the estrogen moiety, and 14C-E2 or 2) as doubly labeled Estracyt with 3H in the E2 and 14C in the carbamate part. These studies were performed in the human and baboon, with biliary excretion studies being performed in the latter. In the human studies with singly labeled Estracyt, it was shown that about 10-15% of the compound is hydrolyzed in such a fashion as to yield E2, which is then metabolized and conjugated similarly to the 14C-labeled E2; and that the excretory pattern in the urine of the released E2, including the CCD pattern, did not differ materially from that of the 14C-E2, though it was excreted at about 1/3 the rate of the 14C-E2. The remainder of the injected Estracyt was not accounted for. No intact Estracyt was found in the urine. When doubly labeled Estracyt was administered to human subjects, it was shown that the excretion of the 14C (carbamate moiety) was much lower than that of the 3H (E2 moiety), indicating that hydrolysis of the molecule did, in fact, take place, but that the excretion of the 14C, as well as the rest of Estracyt, must follow a route other than the urine. The most likely route is the biliary excretion of either intact Estracyt and/or its metabolites and conjugates without any significant enterohepatic circulation, with the bulk ultimately being excreted in the stools. The studies in the baboon mirrored those in the human. We were able, however, to demonstrate substantial excretion of singly and doubly labeled Estracyt in the bile, indicating that this may be the major route by which the compound is excreted in the baboon and, by analogy, in the human.
雌莫司汀，一种雌二醇 - 17β（E2）与氮芥的共轭物，是一种最近被发现对前列腺癌治疗有价值的化合物。本研究关注标记雌莫司汀的去向，其给药方式为：1）作为雌激素部分标记有³H的³H - 雌莫司汀与¹⁴C - E2的混合物；2）作为在E2部分标记有³H且在氨基甲酸酯部分标记有¹⁴C的双标记雌莫司汀。这些研究在人类和狒狒身上进行，对狒狒还进行了胆汁排泄研究。在对单标记雌莫司汀的人体研究中，结果表明约10 - 15%的化合物以产生E2的方式水解，然后其代谢和结合过程与¹⁴C标记的E2相似；释放出的E2在尿液中的排泄模式，包括结合型/游离型模式，与¹⁴C - E2的排泄模式没有实质性差异，尽管其排泄速率约为¹⁴C - E2的1/3。注射的雌莫司汀其余部分去向不明。尿液中未发现完整的雌莫司汀。当给人体受试者注射双标记雌莫司汀时，结果表明¹⁴C（氨基甲酸酯部分）的排泄量远低于³H（E2部分）的排泄量，这表明分子确实发生了水解，但¹⁴C以及雌莫司汀的其余部分必定通过非尿液途径排泄。最可能的途径是完整的雌莫司汀和/或其代谢产物及结合物经胆汁排泄，且没有明显的肠肝循环，大部分最终随粪便排出。在狒狒身上的研究结果与人体研究相似。然而，我们能够证明单标记和双标记雌莫司汀在胆汁中有大量排泄，这表明这可能是该化合物在狒狒以及类推在人体中的主要排泄途径。
