Transport and metabolism of dexamethasone in the dually perfused human placenta.
Dexamethasone (DEX), a synthetic glucocorticoid, has been suggested to accelerate fetal lung maturation and is sometimes used clinically during premature labor for this purpose. These experiments were initiated to measure the rate of transfer and metabolism of DEX by the human placenta. Lobules from full term (38-41 weeks) human placentas, obtained immediately after delivery, were perfused on both maternal and fetal sides. Radiolabeled (14C) DEX and tritiated water were infused into the maternal artery. Samples were taken at timed intervals throughout the perfusion period from the maternal artery (MA), maternal vein (MV), fetal artery (FA) and fetal vein (FV). Transport was determined by liquid scintillation spectroscopy and metabolism of DEX was determined by reversed phase HPLC. Tritiated water reached equilibrium between the maternal and fetal circulations within 75 min of perfusion, while total 14C-labeled radioactivity attained equilibrium after 180 min. HPLC revealed one metabolite of DEX which co-migrated with an 11-ketobetamethasone standard. The concentration of metabolite at 10, 30, 120, and 240 min in the FV were 9, 22, 40, and 41 ng/ml, respectively, and in the MV were 15, 28, 46, and 48 ng/ml, respectively. However, the ratio of metabolite/DEX was greater at 10 min in the FV (0.39) than in the MV (0.08). These data suggest that DEX crosses the human term placenta, that an enzyme in the placenta metabolizes DEX into an 11-keto-metabolite, and that a greater metabolite:DEX ratio is found at earlier times in the fetal circulation than in the maternal circulation.
Smith
M A
MA
Division of Reproductive and Developmental Toxicology, National Center for Toxicological Research, Jefferson, Arkansas 72079.
Thomford
P J
PJ
Mattison
D R
DR
Slikker
W
W
D001692:Biological Transport / Q000502:physiology; D002851:Chromatography, High Pressure Liquid; D003907:Dexamethasone / Q000493:pharmacokinetics*; D006801:Humans; D066298:In Vitro Techniques; D010477:Perfusion; D010920:Placenta / Q000378:metabolism*
D003907:Dexamethasone