Adams W P, Hasegawa J, Johnson R N, Haring R C
J Pharm Sci. 1979 Aug;68(8):986-91. doi: 10.1002/jps.2600680818.
The bioequivalence of four conjugated estrogens tablets USP was compared by measurement of seven estrogens or estrogen metabolites in the urine during steady-state dosing in postmenopausal women. Two studies compared three generic products with the innovator's product. The urinary excretion of 17 alpha-dihydroequilin, 17 alpha-dihydroequilenin, and 17 alpha-estradiol were significantly greater in all cases with the innovator's product than with the generic products. Statistically significant differences between products were observed occasionally for other components. The generic products thus were bioinequivalent to the innovator's product, although all products essentially met current compendial specifications. A third study observed no significant differences between three batches of the innovator's product for the seven components. Total conjugated estrogens excretion of all products at the steady state was essentially equal and correlated with neither disintegration time nor dissolution half-time. Bioinequivalence between products is discussed in relation to the need for an improved USP conjugated estrogens monograph. Evidence suggesting the metabolism of a fraction of dosed estrone, equilin, and 17 alpha-dihydroequilin to 17 beta-estradiol, 17 beta-dihydorequilim, and 17 alpha-dihydroequilenin, respectively, is presented.
通过在绝经后女性稳态给药期间测量尿液中的七种雌激素或雌激素代谢物，比较了四种美国药典（USP）结合雌激素片的生物等效性。两项研究将三种仿制药与创新药进行了比较。在所有情况下，创新药产品中17α-二氢马萘雌酮、17α-二氢马萘雌甾酮和17α-雌二醇的尿排泄量均显著高于仿制药产品。其他成分偶尔也会观察到产品之间的统计学显著差异。因此，尽管所有产品基本符合现行药典标准，但仿制药与创新药产品生物不等效。第三项研究观察到创新药产品的三批样品在七种成分上无显著差异。所有产品在稳态时结合雌激素的总排泄量基本相等，且与崩解时间和溶解半衰期均无相关性。结合改进USP结合雌激素专论的必要性，讨论了产品之间的生物不等效性。文中提供了证据表明，部分给药的雌酮、马萘雌酮和17α-二氢马萘雌酮分别代谢为17β-雌二醇、17β-二氢马萘雌醇和17α-二氢马萘雌甾酮。
