Patel J, Katovich M J, Sloan K B, Curry S H, Prankerd R J
Department of Pharmaceutics, University of Florida, Gainesville 32610, USA.
J Pharm Sci. 1995 Feb;84(2):174-8. doi: 10.1002/jps.2600840210.
The O-saccharinylmethyl prodrug of 17 beta-estradiol was about nine times as potent, based on 50% effective dose (ED50) values, as 17 beta-estradiol when each was given as an oral dose to ovariectomized rats. Similarly, a significant lowering of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels at 24 h was observed when an ED50 dose of the prodrug was given but not when an equimolar dose of 17 beta-estradiol was given orally. However, when given intravenously, there was no difference in potency between the two drugs. In the bioavailability studies, a significantly longer half-life (approximately 5-7 times) for 17B-estradiol was observed when the prodrug was given orally than when 17 beta-estradiol was given orally or when the prodrug or 17 beta-estradiol were given intravenously. This result was consistent with an observed five-fold enhancement in the oral bioavailability of 17 beta-estradiol when the prodrug was given.
基于半数有效剂量（ED50）值，17β-雌二醇的O-糖精甲基前药在给去卵巢大鼠口服时的效力约为17β-雌二醇的九倍。同样，当给予前药的ED50剂量时，在24小时观察到促卵泡激素（FSH）和促黄体生成素（LH）水平显著降低，但口服等摩尔剂量的17β-雌二醇时未观察到这种情况。然而，静脉给药时，两种药物的效力没有差异。在生物利用度研究中，口服前药时观察到17β-雌二醇的半衰期显著延长（约5至7倍），这比口服17β-雌二醇时或静脉给予前药或17β-雌二醇时都要长。这一结果与给予前药时观察到的17β-雌二醇口服生物利用度提高五倍相一致。
