Human pharmacokinetics of ethynyl estradiol 3-sulfate and 17-sulfate.
Pharmacokinetic parameters of ethynyl estradiol 3-sulfate (EE-3) and 17-sulfate (EE-17) were estimated. Each sulfate was administered orally and intravenously to five ovariectomized volunteer women. Blood samples were taken over a period of 24 h. Radioimmunoassay for free and sulfoconjugated ethynyl estradiol (EE) was performed. The analysis of the plasma concentrations obtained after administration of EE-3 and EE-17 indicates significant differences in their pharmacokinetic profiles. EE-3 is cleared more rapidly from the central compartment (systemic circulation), which may indicate that differences in protein binding, tissue binding, metabolism, and distribution exist between EE-3 and EE-17. It has been suggested that these conjugates are a slow-release reservoir for maintenance of blood levels of free EE itself. However, previous studies in baboons have shown that the half-lives of the free and sulfoconjugated EE are similar (ranging from 8.8 to 11.2 h), which is not consistent with this hypothesis. The t1/2 beta (mean 9.28 h) of the 17-sulfate after IV administration was almost identical in women and baboons, and similar to the t1/2 beta of free EE, confirming the previous observation. Only 3.4% of IV and 11.4% of the orally administered 17-sulfate appeared in the blood as free EE; with the 3-sulfate, the conversions were 13.7 and 20.7%, respectively, suggesting that these sulfates are not important slow-release reservoirs. The similarity of pharmacokinetic parameters between women and baboons suggests that this species of nonhuman primate is, in important respects, a suitable animal model for clinical pharmacology.
Goldzieher
J W
JW
Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX 77030.
Mileikowsky
G
G
Newburger
J
J
Dorantes
A
A
Stavchansky
S A
SA
D000284:Administration, Oral; D000328:Adult; D004305:Dose-Response Relationship, Drug; D004997:Ethinyl Estradiol / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D010052:Ovariectomy; D013997:Time Factors
C025810:ethinylestradiol-3-sulfate; D004997:Ethinyl Estradiol; C059147:ethinyl estradiol-17-sulfate