Xenobiotica ( IF 1.8 ) Pub Date : 2020-09-16 , DOI: 10.1080/00498254.2020.1819579 Guangfei Wang 1 , Qiaofeng Ye 1 , Yidie Huang 1 , Jinmiao Lu 1 , Hong Xu 2 , Zhiping Li 1
Abstract
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Juvenile dermatomyositis (JDM) is a rare systemic autoimmune disease specifically affecting children. Mycophenolate mofetil (MMF) is an immunosuppressant used to treat JDM. Mycophenolic acid (MPA) is an active metabolite of MMF. This study aimed to develop a population pharmacokinetic (PPK) model of MPA in children with JDM and optimize the limited sampling strategy (LSS).
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Fifteen JDM patients treated with MMF, at a median age of 7.35 (range, 3.09–16.1) years, were included. Blood samples were collected at 30 minutes pre-dose, 20 minutes, 60 minutes and 180 minutes post-dose to measure the MPA concentrations. Data were retrospectively collected from the electronic medical records. A two-compartment model with first-order absorption, lag time in absorption, and first-order elimination was developed. Height and co-administered cotrimoxazole were added as the covariates to the model.
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Concentrations at different time points were simulated and area under the concentration–time curve (AUC0–12 h) was calculated. By removing one sampling point at a time, AUC0–12 h from three-point sampling strategy was re-calculated via Bayesian approach. AUC0–12 h from the three-point sampling strategy (by removing the point at 20 minutes post-dose) had the strongest correlation with AUC0–12 h from the four-point sampling strategy (Pearson’s r = 0.971).
中文翻译:
小儿皮肌炎患者霉酚酸的群体药代动力学和有限采样策略的优化。
摘要
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青少年皮肌炎(JDM)是一种罕见的全身性自身免疫性疾病,专门影响儿童。霉酚酸酯(MMF)是一种用于治疗JDM的免疫抑制剂。麦考酚酸(MPA)是MMF的活性代谢产物。这项研究旨在建立JDM儿童MPA的群体药代动力学(PPK)模型,并优化有限采样策略(LSS)。
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纳入了15例接受MMF治疗的JDM患者,中位年龄为7.35(范围:3.09-16.1)岁。给药前30分钟,给药后20分钟,60分钟和180分钟收集血液样品以测量MPA浓度。从电子病历中回顾性收集数据。建立了具有一阶吸收,吸收滞后时间和一阶消除的两室模型。将身高和共同给药的考特莫唑作为协变量添加到模型中。
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模拟了不同时间点的浓度,并计算了浓度-时间曲线下的面积(AUC 0-12 h)。通过一次删除一个采样点,可以通过贝叶斯方法重新计算三点采样策略的AUC 0-12小时。三点采样策略中的AUC 0-12小时(通过在给药后20分钟移除点)与四点采样策略中的AUC 0-12小时具有最强的相关性(Pearson r = 0.971)。