Division of Maternal Fetal Medicine, Department of Obstetric and Gynecology, University of Illinois at Chicago, Chicago, IL, USA.
Am J Obstet Gynecol. 2010 Sep;203(3):254.e1-12. doi: 10.1016/j.ajog.2010.06.029.
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.
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.
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.
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.
本研究旨在评估大产科人群中标准剂量倍他米松的药代动力学参数,并评估母体体型和多胎妊娠对药代动力学参数及其观察到的变异性的影响。
这是一项前瞻性药代动力学研究。采用液相色谱-质谱法测定倍他米松的血浆浓度。采用混合效应模型估算药代动力学参数和显著的临床协变量。自举分析验证了模型的有效性。
从 77 名患者中获得了 274 份血样。母体瘦体重(LBW)对药代动力学变异性的影响最大。药代动力学参数与 LBW 的关系在母体体型广泛范围内呈线性关系。多胎妊娠并不影响药代动力学参数。
根据母体 LBW 个体化倍他米松剂量可降低药物暴露的变异性。多胎妊娠不需要倍他米松剂量调整,因为其药代动力学与单胎妊娠相同。