Distribution of dexamethasone between mother and fetus after maternal administration.

Abstract

Summary: The adrenal glucocorticoid hormones are believed to have an important role in the definitive biochemical differentiation of a number of fetal organs. This paper presents data for dexamethasone transfer and distribution between mother and fetus using 20-21 days pregnant rats. This synthetic glucocorticoid is rapidly transferred to the fetus and reaches a plateau by 90 min after administration to the mother. Pregnant rats receiving either a high dose (20 mg) or a low dose (2.2 µg) had almost identical concentration distribution ratios with a mean of 0.311 (± 0.013) and 0.332 (± 0.019) between fetal and maternal plasmas, respectively. In vitro binding measured by equilibrium dialysis showed that maternal plasma bound only 4-5% more than the fetal plasma. Essentially no radioactivity remained bound to protein after Sephadex G-50 chromatography, indicating no high affinity sites for dexamethasone in either maternal or fetal plasma. Acetylation of ethyl acetate extracts of fetal and maternal plasma followed by paper chromatograph revealed two identical peaks for both the dexamethasone standard and the plasma radioactivity. This study demonstrates a rapid transfer of administered dexamethasone from the mother to the fetus with a concentration difference between the two plasma pools. The difference in concentration does not appear to be the result of differential protein binding or metabolism. Speculation: The rat placenta would appear to maintain an appreciable concentration difference between maternal and fetal plasma for the glucocorticoid hormones. The nature of the process which accounts for this phenomenon needs further investigation.