Chandrasekaran A, Osman M, Scatina J A, Sisenwine S F
Drug Metabolism Division, Wyeth-Ayerst Research, Princeton, NJ 08543, USA.
J Steroid Biochem Mol Biol. 1995 Nov;55(2):271-8. doi: 10.1016/0960-0760(95)00161-r.
The metabolism of equilin sulfate was determined in female dogs receiving 2.5 mg/kg of [3H]equilin sulfate alone or in a preparation that contained all the components that are present in the conjugated equine estrogen product Premarin. The pharmacokinetic parameters of total radioactivity indicated that the drug is rapidly absorbed and it has a moderate half-life in plasma. The total radioactivity in plasma following administration of [3H]equilin sulfate as part of a mixture of conjugated equine estrogens had significantly lower peak concentration (Cmax), a lower area under the curve (AUC), a longer terminal half-life (t1/2) and a longer mean residence time (MRT) than when [3H]equilin sulfate was given alone, indicating that the other components in the conjugated equine estrogen preparation altered the pharmacokinetics of equilin sulfate. An average of 26.7 +/- 4.4% of the administered radioactive dose was excreted in urine of dogs receiving [3H]equilin sulfate. Again, a significantly lower percentage (21.4 +/- 6.3%, P = 0.023) was eliminated in urine of dogs receiving [3H]equilin sulfate in the conjugated equine estrogen preparation, indicating that the absorption of equilin sulfate was perhaps altered by the other components in the conjugated equine estrogen preparation. Metabolite profiles of plasma and urine were similar. Equilin, equilenin, 17 beta-dihydroequilenin, 17 beta-dihydroequilin, 17 alpha-dihydroequilenin and 17 alpha-dihydroequilin were present in both matrices. 17 beta-Dihydroequilin and equilin were the two major chromatographic peaks in plasma samples. 17 beta-Dihydroequilenin and 17 beta-dihydroequilin were the major metabolites in urine. In conclusion, following oral administration of [3H]equilin sulfate to dogs, the radioactivity is rapidly absorbed. The disposition of equilin sulfate is altered by the other components that are present in the conjugated equine estrogen preparation Premarin. The reduction of the 17-keto group and aromatization of ring-B are the major metabolic pathways of equilin in the dog.
在单独接受2.5mg/kg [3H]硫酸马萘雌酮的雌性犬，或接受含有结合型马雌激素产品倍美力中所有成分制剂的雌性犬中，对硫酸马萘雌酮的代谢情况进行了测定。总放射性的药代动力学参数表明，该药物吸收迅速，在血浆中有适度的半衰期。作为结合型马雌激素混合物一部分给予[3H]硫酸马萘雌酮后，血浆中的总放射性具有显著更低的峰浓度（Cmax）、更低的曲线下面积（AUC）、更长的末端半衰期（t1/2）和更长的平均驻留时间（MRT），这表明结合型马雌激素制剂中的其他成分改变了硫酸马萘雌酮的药代动力学。接受[3H]硫酸马萘雌酮的犬，平均有26.7±4.4%的给药放射性剂量经尿液排出。同样，接受结合型马雌激素制剂中[3H]硫酸马萘雌酮的犬经尿液排出的百分比显著更低（21.4±6.3%，P = 0.023），这表明结合型马雌激素制剂中的其他成分可能改变了硫酸马萘雌酮的吸收。血浆和尿液的代谢物谱相似。马萘雌酮、马萘雌酚、17β-二氢马萘雌酚、17β-二氢马萘雌酮、17α-二氢马萘雌酚和17α-二氢马萘雌酮在两种基质中均有存在。17β-二氢马萘雌酮和马萘雌酮是血浆样本中的两个主要色谱峰。17β-二氢马萘雌酚和17β-二氢马萘雌酮是尿液中的主要代谢物。总之，给犬口服[3H]硫酸马萘雌酮后，放射性迅速吸收。硫酸马萘雌酮的处置被结合型马雌激素制剂倍美力中存在的其他成分改变。17-酮基的还原和B环的芳构化是犬体内马萘雌酮的主要代谢途径。
