Transplacental Pharmacokinetics and Metabolism of Diethylstilbestrol and 17β-Estradiol in the Pregnant Rhesus Monke*
| Autor: | Thomas J. Sziszak, William Slikker, Donald E. Hill, Edward D. Helton, George W. Lipe, Glenn D. Newport, John R. Bailey |
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| Rok vydání: | 1980 |
| Předmět: |
medicine.medical_specialty
Placenta Endocrinology Diabetes and Metabolism Metabolite Clinical Biochemistry Diethylstilbestrol Tritium Biochemistry Mass Spectrometry chemistry.chemical_compound Endocrinology Pharmacokinetics Pregnancy Internal medicine medicine Animals Carbon Radioisotopes Fetus Estradiol Biochemistry (medical) Transplacental Haplorhini Macaca mulatta Kinetics medicine.anatomical_structure Fetal circulation chemistry Fetoplacental Circulation Female medicine.drug |
| Zdroj: | The Journal of Clinical Endocrinology & Metabolism. 50:811-818 |
| ISSN: | 1945-7197 0021-972X |
| Popis: | Experiments were performed to describe and compare the transplacental pharmacokinetics of the teratogen and transplacental carcinogen, diethylstilbestrol [4,4'-dihydroxy-alpha,alpha'-diethyl-trans, cis-stilbene (DES)], and the endogenous estrogen, 17 beta-estradiol (E2). Timed mated pregnant rhesus monkeys (119-137 days gestation) were anesthetized, and catheters were implanted in the maternal femoral artery and the interplacental fetal artery and vein using an extraamniotic technique. Single doses of either radiolabeled DES or E2 were administered via the maternal radial vein. Maternal plasma levels of labeled compound decreased rapidly after dose administration. Fetal plasma levels of radioactivity derived from either DES or E2 increased rapidly and then plateaued higher than maternal levels 1--2 h after dose administration. High pressure liquid chromatography of maternal and fetal plasma samples revealed both parent and conjugated metabolites of DES and E2. The principal metabolite of DES (DES monglucuronide) was radiolabeled and given to either the mother or the fetus iv. There was no significant cross-over of this metabolite in either direction. It is concluded that DES crosses the primate placenta in an unconjugated form and that, based on total radioactivity, placental transfer is similar to that of E2. The extensive fetoplacental metabolism of DES appears to be responsible for the greater half-life of this agent and its metabolites in the fetal circulation compared with the maternal circulation. |
| Databáze: | OpenAIRE |
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