Newburger J, Castracane V D, Moore P H, Williams M C, Goldzieher J W
Am J Obstet Gynecol. 1983 May 1;146(1):80-7. doi: 10.1016/0002-9378(83)90931-6.
Ethinyl estradiol sulfates are major circulating metabolites of ethinyl estradiol (EE2); this is a relationship analogous to that of endogenous estrone and estrone sulfate. Because of the wide use of contraceptives containing EE2, the pharmacokinetics of its sulfate conjugates are of some importance. In previous studies of the intermediate metabolism of ethinyl estrogens we have shown that the baboon is an appropriate animal model. Accordingly, oral and/or intravenous doses of EE2 or each of its three sulfates were administered to castrate female baboons, and plasma levels of EE2 and its sulfates were studied by specific radioimmunoassay or radioisotope counting. After intravenous administration of EE2, the 3-sulfate and the 3,17-disulfate are the major circulating metabolites. After oral dosage administration, the 3-glucuronide and, in some cases, the 3,17-diglucuronide also become important. After intravenous administration, about twice as much of the drug exists in the sulfate as in the free form, as reflected by the areas under the plasma level curves. The bioavailability of orally administered EE2 was about 60%, confirming the presence of a substantial first-pass effect. Hydrolysis at the 17-position occurs when EE2-17-sulfate is administered orally but appears not to occur with intravenous administration. EE2 and the three sulfates, given intravenously, exhibited two-compartment open-model kinetics. The elimination phase half-lives of all four compounds were similar, ranging from 8.8 to 11.2 hours. The area under the plasma level curve of EE2 resulting from the intravenous administration of the 3-sulfate was approximately 8% of the total area under the plasma level curve of both EE2 and EE2 sulfates. The ratio of the area under the plasma level curve of sulfates resulting from 3-sulfate administration compared to the other two sulfates was approximately 0.3, reflecting the existence of other metabolic pathways for its disposition.
炔雌醇硫酸盐是炔雌醇（EE2）的主要循环代谢产物；这种关系类似于内源性雌酮和硫酸雌酮的关系。由于含 EE2 的避孕药广泛使用，其硫酸盐共轭物的药代动力学具有一定重要性。在先前关于炔雌醇中间代谢的研究中，我们已表明狒狒是合适的动物模型。因此，给去势雌性狒狒口服和/或静脉注射 EE2 或其三种硫酸盐中的每一种，并通过特异性放射免疫测定或放射性同位素计数研究 EE2 及其硫酸盐的血浆水平。静脉注射 EE2 后，3 - 硫酸盐和 3,17 - 二硫酸盐是主要的循环代谢产物。口服给药后，3 - 葡萄糖醛酸苷以及在某些情况下的 3,17 - 二葡萄糖醛酸苷也变得重要。静脉注射后，血浆水平曲线下的面积反映出约两倍的药物以硫酸盐形式存在而非游离形式。口服 EE2 的生物利用度约为 60%，证实存在显著的首过效应。口服 EE2 - 17 - 硫酸盐时在 17 位发生水解，但静脉注射时似乎不发生。静脉注射 EE2 和三种硫酸盐呈现二室开放模型动力学。所有四种化合物的消除相半衰期相似，范围为 8.8 至 11.2 小时。静脉注射 3 - 硫酸盐产生的 EE2 的血浆水平曲线下面积约为 EE2 和 EE2 硫酸盐的血浆水平曲线下总面积的 8%。3 - 硫酸盐给药产生的硫酸盐的血浆水平曲线下面积与其他两种硫酸盐相比的比率约为 0.3，反映出其处置存在其他代谢途径。
