Determination of Plasma Dexamethasone in the Mother and the Newborn after Administration of the Hormone in a Clinical Trial

Abstract

A RIA method is described for the measurement of dexamethasone in maternal, cord, and neonate plasma in a collaborative multicenter clinical trial to evaluate the efficacy of antenatal steroid therapy in the prevention of respiratory distress syndrome. The antiserum raised against dexamethasone-3-carboxymethyloxime-BSA conjugate was highly specific in that the endogenous steroids and 11-dehydrodexamethasone, a metabolite of dexamethasone, had a cross-reaction of less than 2.0%. Both pregnancy and cord plasma had to be purified by either gel filtration and/or paper chromatography. The overall recoveries of dexamethasone were 75.3 +/- 6.7% and 48.9 +/-6.7% for maternal and cord plasma samples, respectively. The intra- and interassay coefficients of variance for maternal plasma were 8.4% ad 9.1%, respectively, and for cord plasma were 11.9% and 10.9%, respectively. There was a good correlation between the dexamethasone values obtained by RIA when compared with those obtained by performance liquid chromatography in some cord plasma specimens. The recoveries of added dexamethasone and its metabolite by high performance liquid chromatography were also found to be good. The average maternal plasma dexamethasone level was 37 ng/ml 2 h after im injections of 5 mg dexamethasone phosphate every 12 h. The half-life of dexamethasone measured after the discontinuation of the drug was 216 min. Dexamethasone appeared too be cleared very rapidly from the circulation of the fetus and neonate. Because 11-dehydrodexamethasone was not present in significant amounts in the neonate, it was concluded that other factors in addition to the conversion of dexamethasone to its 11 dehydro metabolite were responsible for the rapid clearance of dexamethasone from fetal and neonatal circulation.

Pituitary-Adrenal Responses to Acute Hypoxemia During and After Maternal Dexamethasone Treatment in Sheep

“…The plasma concentrations of dexamethasone measured in fetal sheep were similar to values measured in human umbilical cord blood within 24 h of a course of antenatal glucocorticoid therapy (13,14). Although maternal injection with dexamethasone would have exposed the ewe and the fetus to initially high then rapidly decreasing concentrations of synthetic glucocorticoid, the plasma concentrations in maternal and fetal blood at the onset of H1 were similar to those reported previously 8 h after injection in the pregnant ewe and the fetus (15) and to those reported in the fetus after 24 h of direct i.v.…”

Influence of protein‐calorie malnutrition on the pharmacokinetics, placental transfer and tissue localization of dexamethasone in rats

“…However, a contributory role of PCMinduced decrease in dexamethasone metabolism in the prolongation of its plasma half-life cannot be excluded. The finding that dexamethasone level in the foetal serum did not exceed 40% of that in the maternal serum for long periods is in conformity with data on the maternal-foetal exchange of this agent in rats (Funkhouser etal., 1978), sheep (Bayard etal., 1972;Anderson et al, 1979) and man (Kream et al, 1983) as well as with data on the transplacental passage of other synthetic glucocorticoids such as triamcinolone acetonide (Slikker etal., 1982), betamethasone (Ballard et al, 1975) and prednisolone (Beitins et al, 1972). Because the binding of dexamethasone to maternal and foetal serum proteins is not different as has also been reported by others (Funkhouser et al, 1978) and its metabolism by the placenta is insignificant, it seems improbable that significantly lower foetal than maternal serum dexamethasone concentrations are maintained by these factors.…”

“…The suitability of the protocol for inducing PCM Varma & Yue, 1983) and of the techniques for the quantitation of dexamethasone by radioimmunoassay (Varma & Mulay, 1980) and by h.p.l.c. (Kream et al, 1983) have been described previously. However, the transplacental passage of dexamethasone was not determined at steady-state conditions.…”

“…At the end of the incubation, samples were extracted with methylene chloride and assayed for dexamethasone and metabolite(s) by h.p.l.c. (Kream et al, 1983).…”

“…Dexamethasone and 11-dehydrodexamethasone in placental minces were measured by h.p.l.c. (Kream et al, 1983) by means of a pBondapak C18 reverse-phase column (Waters) and a mobile phase of acetonitrile: methanol: water (25:25:50) at a flow rate of 1 ml min-delivered by an Altex pump (Varma & Yue, 1983). Prednisolone was used as the internal standard and the absorbance was measured at 254 nm.…”