Disposition of betamethasone in parturient women after intravenous administration

Summary

The pharmacokinetics of betamethasone and its phosphate ester are described in nine women in late pregnancy who each received a bolus intravenous dose of 10.6 mg betamethasone phosphate. Both compounds were measured by high-performance liquid chromatography with ultra-violet detection using sample handling methods which prevent in vitro hydrolysis of the ester. The plasma clearance of betamethasone phosphate (mean=980 ml/min) and its apparent distribution volume (mean=5.61) were both higher than previously found for nonpregnant subjects, but its half-life (mean=4.6 min) was unchanged. Plasma concentrations of betamethasone reached a peak 5–37 min after dosing with betamethasone phosphate, then declined biexponentially with a mean terminal half-life of 262 min. Plasma clearance in pregnant patients (mean=287 ml/min) was higher than previously reported for nonpregnant subjects. Evidence from urinary excretion and plasma binding measurements and the previously reported transplacental plasma concentration gradient indicated that the increase in clearance was due to increased metabolism possibly by the placental/fetal unit. Plasma binding of betamethasone was higher in maternal than fetal plasma; binding to α₁-acid glycoprotein was more important than binding to albumin as a determinant of this difference. In pregnant patients the decline of endogenous cortisol concentrations in maternal venous plasma was less marked and slower than in nonpregnant subjects. The data now available allows comparison of pharmacokinetic properties between betamethasone and its stereoisomer dexamethasone with respect to their use in preventing neonatal respiratory distress syndrome.