title: Influence of streptozotocin-diabetes on the pharmacokinetics, placental transfer and tissue localization of dexamethasone in rats.
abstract: The influence of streptozotocin-diabetes on the pharmacokinetics, placental transfer and tissue localization of dexamethasone was determined in Sprague-Dawley rats. Diabetes significantly increased the volume of distribution of dexamethasone in pregnant but not in nonpregnant rats; plasma half-life was not significantly increased. Concentrations of maternally administered dexamethasone in all tissues studied (maternal and foetal serum and livers, foetal lungs and placentas) except the amniotic fluid were lower in diabetic than in control animals. Diabetes did not alter the binding of dexamethasone to maternal or foetal serum proteins. Insulin treatment partially reversed the effects of diabetes on the maternal-foetal exchange of dexamethasone. Diabetes-induced decrease in the foetal localization of dexamethasone appears to be caused by a decrease in the maternal serum levels as well as by an increase in the foetal excretion of the steroid into the amniotic fluid. In so far as the rat model reflects the human situation, the present data suggest that a standard dose of dexamethasone might not be adequate in promoting foetal lung maturation in diabetic pregnancies.
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D003907:Dexamethasone / Q000097:blood / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D013347:Subcellular Fractions / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D001798:Blood Proteins; D007328:Insulin; D003907:Dexamethasone