Betamethasone in pregnancy: influence of maternal body weight and multiple gestation on pharmacokinetics

• Published in: American journal of obstetrics and gynecology 2010-09, Vol.203 (3), p.254.e1-254.e12
• Main Authors: Della Torre, Micaela, MD, MS, Hibbard, Judith U., MD, Jeong, Hyunyoung, PharmD, PhD, Fischer, James H., PharmD
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; antenatal steroid; Area Under Curve; Bayes Theorem; betamethasone; Betamethasone - blood; Betamethasone - pharmacokinetics; Biological and medical sciences; Body Mass Index; Body Weight; Bones, joints and connective tissue. Antiinflammatory agents; Chromatography, Liquid; Female; Glucocorticoids - blood; Glucocorticoids - pharmacokinetics; Gynecology. Andrology. Obstetrics; Humans; Medical sciences; Middle Aged; Obstetrics and Gynecology; pharmacokinetics; Pharmacology. Drug treatments; Pregnancy; Pregnancy, Multiple; prematurity; Prospective Studies; Tandem Mass Spectrometry
• ISSN: 0002-9378; 1097-6868
• DOI: 10.1016/j.ajog.2010.06.029

Objective The goals of the study were to estimate the pharmacokinetic parameters of standard dose betamethasone in a large obstetrics population and evaluate the effect of maternal body size and multiple gestation on the pharmacokinetic parameters and their observed variability. Study Design This was a prospective pharmacokinetic study. Liquid chromatography mass spectrometry was used to measure betamethasone plasma concentrations. Pharmacokinetic parameters and significant clinical covariates were estimated with mixed effect modeling. Bootstrap analysis confirmed validity of the model. Results Two hundred seventy-four blood samples from 77 patients were obtained. The greatest effect on pharmacokinetic variability was observed with maternal lean body weight (LBW). The relationship between the pharmacokinetic parameters and LBW remained linear over a wide range of maternal body sizes. Multiple gestations did not affect the pharmacokinetic parameters. Conclusion Individualization of betamethasone dosing by maternal LBW reduces variability in drug exposure. Mutiple gestations do not require betamethasone dosing adjustment, because pharmacokinetics are the same as singleton gestations.