马结合雌激素的药代学和药效学:化学和代谢。
文章的细节
-
引用
复制到剪贴板 -
Bhavnani BR
马结合雌激素的药代学和药效学:化学和代谢。
Proc Soc实验医学杂志。1998年1月,217 (1):-。
- PubMed ID
-
9421201 (在PubMed]
- 文摘
-
马结合雌激素(结合雌激素),广泛用于雌激素替代疗法和预防绝经后妇女的骨质疏松症和心血管疾病。结合雌激素包含至少10雌激素的硫酸酯B环饱和雌激素:雌激素、17个beta雌二醇,17 alpha-estradiol,和B环不饱和雌激素:equilin, 17 beta-dihydroequilin 17 alpha-dihydroequilin equilenin, 17 beta-dihydroequilenin 17 alpha-dihydroequilenin, delta-8-estrone。生物和雌激素受体结合的研究表明,所有10个雌激素生物活性。此外,单个组件,如硫酸equilin, delta-8-estrone硫酸,硫酸17 beta-dihydroequilin和雌激素酮硫酸盐,强有力的雌激素效应。雌激素硫酸盐可以直接从胃肠道吸收;然而,水解的硫酸盐也发生在胃肠道,和非结合的雌激素形成很容易吸收。迅速吸收后,这些雌激素是硫酸和流通形式。这些雌激素的药物动力学表明,非结合的雌激素被清除的流通速度比硫酸酯的形式。在绝经后妇女,这些雌激素代谢的17-keto衍生品17 beta-reduced产品更有效。这个激活的程度几乎是与一些B环不饱和雌激素高出10倍。 The 17beta-reduced metabolites are cleared from the blood at a slower rate than their corresponding 17-keto derivatives. In the human endometrium, equilin is metabolized to 2-hydroxy and 4-hydroxy equilin, with 2-hydroxylation being predominant. In contrast, 2-hydroxy and 4-hydroxy estradiol are formed in equal amounts. Similarly, 16alpha-hydroxylation occurs with both types of estrogens; however, with the ring B saturated estrogens, the 17-keto steroid 16alpha-hydroxy estrone was the major urinary metabolite, whereas with the ring B unsaturated estrogens, the 17beta-reduced steroids, such as 16alpha-hydroxy-17beta-dihydroequilin and 16alpha-hydroxy-17beta-dihydroequilenin, were the major metabolites. This difference in metabolism may be important as it has been suggested that 16alpha-hydroxy estrone (alpha-ketol structure) can form covalent adducts with macromolecules and that it may be oncogenic. These types of interactions will not occur with the 16alpha-hydroxylated-17beta-reduced metabolites of ring B unsaturated estrogens. Since all of the estrogens present in Premarin have estrogenic activity, the pharmacological effects of Premarin are a result of the sum of these individual activities. Therefore, preparations lacking some of these important components may not offer the same degree of beneficial effects as Premarin.
