Brookfield Kathleen, Galadanci Hadiza, Du Lihong, Wenning Larissa, Mohammed Idris, Suleiman Maryam, Oladapo Olufemi T, Witjes Han, Carvalho Brendan
Division of Perinatology, Oregon Health & Science University, Portland, OR (Dr Brookfield).
Department of Obstetrics & Gynaecology, Aminu Kano Teaching Hospital, Bayero University, Kano, Nigeria (Dr Galadanci).
AJOG Glob Rep. 2021 Aug 28;1(4):100018. doi: 10.1016/j.xagr.2021.100018. eCollection 2021 Nov.
Current intramuscular magnesium dosing regimens in low and middle-income countries are based on indirect absorption parameters to inform pharmacokinetic and pharmacodynamic response.
To determine if therapeutic serum magnesium levels are obtained in women with severe preeclampsia receiving intramuscular administration of magnesium sulfate using the Pritchard regimen and to compare the key pharmacokinetic variables to those previously published.
Serum magnesium levels were obtained at multiple time points at baseline and after magnesium sulfate administration from women with severe preeclampsia receiving the standard Pritchard regimen for seizure prophylaxis at Bayero University, Kano, Nigeria. The pharmacokinetic profiles were constructed for the study cohort and the updated pharmacokinetic model was compared with the one that was previously published.
A total of 80 blood samples were collected from 20 women with severe preeclampsia (45 collected before childbirth and 35 collected after childbirth). After 11.5 hours of magnesium sulfate administration, 63% of women in the cohort had serum magnesium levels of ≥2.0 mmol/L. Data from women receiving the Pritchard regimen combined with data from women previously modeled after the receipt of intravenous magnesium sulfate were adequately described using a 2-compartment model with first-order absorption and linear elimination from the central compartment. All structural pharmacokinetic parameters including clearance, central volume of distribution, peripheral volume of distribution, and intercompartment clearance were adjusted for maternal weight, and the clearance was further adjusted for serum creatinine level and antepartum or postpartum status. The simulated pharmacokinetic profiles of the updated pharmacokinetic model and the previously published pharmacokinetic model are similar. In previously published pharmacokinetic modeling, absorption rate constant=0.32 and absolute bioavailability=0.86. In the updated pharmacokinetic model, absorption rate constant=0.45 and absolute bioavailability=0.91.
These data support the use of the Pritchard regimen as acceptable to achieve therapeutic serum magnesium levels and support the reported simulation of serum magnesium levels and eclampsia response associated with different intramuscular regimens.
低收入和中等收入国家目前的肌内注射镁剂给药方案是基于间接吸收参数来了解药代动力学和药效学反应。
确定使用普里查德方案接受硫酸镁肌内注射的重度子痫前期女性是否能达到治疗性血清镁水平，并将关键药代动力学变量与先前发表的结果进行比较。
在尼日利亚卡诺的巴耶罗大学，对接受标准普里查德方案预防子痫发作的重度子痫前期女性，在基线和硫酸镁给药后的多个时间点获取血清镁水平。为研究队列构建药代动力学曲线，并将更新后的药代动力学模型与先前发表的模型进行比较。
共从20名重度子痫前期女性中采集了80份血样（45份在分娩前采集，35份在分娩后采集）。在硫酸镁给药11.5小时后，队列中63%的女性血清镁水平≥2.0 mmol/L。使用具有一级吸收和中央室线性消除的二室模型，能充分描述接受普里查德方案的女性数据以及先前接受静脉注射硫酸镁后建模的女性数据。所有结构药代动力学参数，包括清除率、中央室分布容积、外周室分布容积和室间清除率，均根据产妇体重进行了调整，清除率还进一步根据血清肌酐水平和产前或产后状态进行了调整。更新后的药代动力学模型与先前发表的药代动力学模型的模拟药代动力学曲线相似。在先前发表的药代动力学建模中，吸收速率常数=0.32，绝对生物利用度=0.86。在更新后的药代动力学模型中，吸收速率常数=0.45，绝对生物利用度=0.91。
这些数据支持使用普里查德方案来达到治疗性血清镁水平，并支持所报道的与不同肌内注射方案相关的血清镁水平模拟和子痫反应。
