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Disposition of synthetic glucocorticoids: II. Dexamethasone in parturient women
Author(s) -
Tsuei S Edmund,
Petersen Marisa C,
Ashley John J,
McBride William G,
Moore R George
Publication year - 1980
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1980.136
Subject(s) - umbilical vein , dexamethasone , venous blood , medicine , bolus (digestion) , fetus , transplacental , endocrinology , placenta , intravenous bolus , pregnancy , chemistry , biology , biochemistry , in vitro , genetics
The plasma level:time profile for dexamethasone after dexamethasone phosphate 8 mg by intravenous bolus (n = 6) or intramuscular injection (n = 6) to pregnant women near term who were to undergo cesarean section was determined by high‐performance liquid chromatography. Although pregnancy did not affect the terminal half‐life (mean, 142 min; n = 10), the estimate of total plasma clearance was greater in pregnant (559 ml/min) than in nonpregnant women (243 ml/min). The umbilical/maternal venous plasma level ratios of dexamethasone rose with time from last dose to delivery, toward a plateau value of about 0.45. Plasma binding was not different between blood from pregnant (66.6% bound, n = 11) and nonpregnant women (68.1% bound, n = 6) but was lower in umbilical vein blood (60.8% bound, n = 11). Blood/plasma level ratio was higher in maternal (0.92, n = 7) and umbilical vein blood (1.04, n = 7) than in blood from nonpregnant subjects (0.81, n = 12). We conclude that the fetus is a slowly equilibrating compartment for dexamethasone and that the transplacental dexamethasone concentration gradient as well as the increased total clearance in the mother near parturition are most likely attributable to metabolic clearance by the placenta. Clinical Pharmacology and Therapeutics (1980) 28, 88–98; doi: 10.1038/clpt.1980.136