足月新生儿亚低温治疗时阿莫西林的群体药代动力学。
Population Pharmacokinetics of Amoxicillin in Term Neonates Undergoing Moderate Hypothermia.
机构信息
Department of Pharmacy, Academic Medical Center, Amsterdam, The Netherlands.
Paediatric Clinical Research Office, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, The Netherlands.
出版信息
Clin Pharmacol Ther. 2018 Mar;103(3):458-467. doi: 10.1002/cpt.748. Epub 2017 Oct 13.
The pharmacokinetics (PK) of amoxicillin in asphyxiated newborns undergoing moderate hypothermia were quantified using prospective data (N = 125). The population PK was described by a 2-compartment model with a priori birthweight (BW) based allometric scaling. Significant correlations were observed between clearance (Cl) and postnatal age (PNA), gestational age (GA), body temperature (TEMP), and urine output (UO). For a typical patient with GA 40 weeks, BW 3,000 g, 2 days PNA (i.e., TEMP 33.5°C), and normal UO, Cl was 0.26 L/h (interindividual variability (IIV) 41.9%) and volume of distribution of the central compartment was 0.34 L/kg (IIV of 114.6%). For this patient, Cl increased to 0.41 L/h at PNA 5 days and TEMP 37.0°C. The respective contributions of both covariates were 23% and 27%. Based on Monte Carlo simulations we recommend 50 and 75 mg/kg/24h amoxicillin in three doses for patients with GA 36-37 and 38-42 weeks, respectively.
采用前瞻性数据（N=125）对接受中度低温治疗的窒息新生儿的阿莫西林药代动力学（PK）进行了量化。采用两室模型描述群体 PK，并以前置体重（BW）为基础进行了体表面积标度。清除率（Cl）与出生后年龄（PNA）、胎龄（GA）、体温（TEMP）和尿量（UO）之间存在显著相关性。对于 GA 为 40 周、BW 为 3000g、PNA 为 2 天（即 TEMP 为 33.5°C）且 UO 正常的典型患者，Cl 为 0.26 L/h（个体间变异度（IIV）为 41.9%），中央室分布容积为 0.34 L/kg（IIV 为 114.6%）。对于该患者，当 PNA 为 5 天且 TEMP 为 37.0°C 时，Cl 增加至 0.41 L/h。这两个协变量的各自贡献分别为 23%和 27%。基于蒙特卡罗模拟，我们建议 GA 分别为 36-37 周和 38-42 周的患者使用 50 和 75mg/kg/24h 的阿莫西林分三剂给药。
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