A pharmacokinetic model for amiodarone in infants developed from an opportunistic sampling trial and published literature data.
A pharmacokinetic model for amiodarone in infants developed from an opportunistic sampling trial and published literature data.
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DOI：
10.1007/s10928-018-9576-y
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发表时间：
2018-06
影响因子：
2.5
通讯作者：
Cohen-Wolkowiez M
中科院分区：
文献类型：
--
作者：
Dallefeld SH;Atz AM;Yogev R;Sullivan JE;Al-Uzri A;Mendley SR;Laughon M;Hornik CP;Melloni C;Harper B;Lewandowski A;Mitchell J;Wu H;Green TP;Cohen-Wolkowiez M
胺碘酮是治疗儿童室颤或室性心动过速的一线抗心律失常药，但其在该人群中的药代动力学（PK）知之甚少。我们使用通过机会性研究设计收集的样本开发了群体PK（PopPK）模型，该研究设计是根据标准治疗接受胺碘酮的儿童，并补充了文献中的胺碘酮PK数据。研究数据和文献数据主要来自2岁以下的婴儿，因此我们的分析仅限于这一组。最终的合并数据集包括45例受试者的266个血浆药物浓度，中位（四分位距）出生后年龄为40.1（11.0-120.4）天，体重为3.9（3.1-5.1）kg。由于相对于成人PopPK研究中估计的终末半衰期，首次给药后的中位采样时间较短（研究：95小时;文献：72小时），因此将深室容积和流量值固定为文献值。三室模型最好地描述了数据，并通过视觉预测检查和非参数Bootstrap分析进行了验证。最终模型将体重作为所有体积以及隔室间和消除清除率的协变量。清除率（CL）、稳态分布容积和终末半衰期的经验贝叶斯估计值分别为0.25（90% CL：0.14-0.36）L/kg/h、93（68-174）L/kg和266（197-477）h。这些研究将为未来在婴儿和儿童中进行胺碘酮的PopPK研究提供有用的信息，从而可以改善剂量方案。
Amiodarone is a first-line antiarrhythmic for life-threatening ventricular fibrillation or ventricular tachycardia in children, yet little is known about its pharmacokinetics (PK) in this population. We developed a population PK (PopPK) model using samples collected via an opportunistic study design of children receiving amiodarone per standard of care supplemented by amiodarone PK data from the literature. Both study data and literature data were predominantly from infants <2 years old, so our analysis was restricted to this group. The final combined dataset consisted of 266 plasma drug concentrations in 45 subjects with a median (interquartile range) postnatal age of 40.1 (11.0–120.4) days and weight of 3.9 (3.1–5.1) kg. Since the median sampling time after the first dose was short (study: 95 hours; literature: 72 hours) relative to the terminal half-life estimated in adult PopPK studies, values of the deep compartment volume and flow were fixed to literature values. A 3-compartment model best described the data and was validated by visual predictive checks and non-parametric bootstrap analysis. The final model included body weight as a covariate on all volumes and on both inter-compartmental and elimination clearances. The empiric Bayesian estimates for clearance (CL), volume of distribution at steady state, and terminal half-life were 0.25 (90% CL: 0.14–0.36) L/kg/h, 93 (68–174) L/kg, and 266 (197–477) h, respectively. These studies will provide useful information for future PopPK studies of amiodarone in infants and children that could improve dosage regimens.
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影响因子：
120.7
作者：
Nadkarni, VM;Larkin, GL;Berg, RA
通讯作者：
Berg, RA
DOI：
10.1016/j.jtcvs.2008.04.011
发表时间：
2008-11-01
影响因子：
6
作者：
Haas, Nikolaus A.;Camphausen, Christoph K.
通讯作者：
Camphausen, Christoph K.
影响因子：
3.6
作者：
Burri, S;Hug, MI;Bauersfeld, U
通讯作者：
Bauersfeld, U
影响因子：
2.8
作者：
Dubin, AM;Van Hare, GF;Rosenthal, DN
通讯作者：
Rosenthal, DN
影响因子：
2.9
作者：
KorthBradey, JM;Rose, GM;Chiang, ST
通讯作者：
Chiang, ST