Comparison of the Transplacental Pharmacokinetics of Estradiol-17Beta and Diethylstilbestrol in the Rhesus Monkey

摘要

In order to determine if transplacental pharmacokinetic differences between the synthetic estrogen, diethylstilbestrol (DES), and the endogenous hormone, estradiol-17 beta (E2) resulted in differential fetal exposure, the two alternately radiolabebeled estrogens were administered simultaneously to late gestational age rhesus monkeys. Under ketamine anesthesia, serial plasma samples were drawn through catheters surgically implanted in the maternal circulation and in the fetal umbilical artery and vein. Similar peak concentrations of total radioactivity derived from DES and E2 were observed in the fetal plasma by 20 min after i.v. maternal administration. HPLC analysis of the plasma samples was used to quantify the radiolabeled estrogens: DES, DES monoglucuronide (DESG) and three other DES derived glucuronide conjugates; E2, estrone (E1), estrone sulfate (E1S) and estrone glucuronide (E1G). The maternal and fetal metabolic profiles were markedly different for estradiol with E1 and E1S predominating in the fetal plasma and E2 and E1G in the maternal. With DES, the profiles were similar except that DES concentration was greater in the fetus as compared to the mother.