未修复法洛四联症婴儿瑞芬太尼的群体药代动力学建模

Population Pharmacokinetic Modeling of Remifentanil in Infants with Unrepaired Tetralogy of Fallot.

作者信息

Chang Jing, Shen Yang, Huang Yue, Sun Ying, Cai Mei-Hua, Niu Jing, Zhang Li-Ming, Zheng Ji-Jian, Zhang Ma-Zhong

机构信息

Department of Anesthesiology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, 1678 Dongfang Rd, Shanghai, 200127, China.

Pediatric Clinical Pharmacology Laboratory, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

Eur J Drug Metab Pharmacokinet. 2019 Feb;44(1):53-62. doi: 10.1007/s13318-018-0489-3.

DOI:10.1007/s13318-018-0489-3

PMID:29915955

Abstract

BACKGROUND

Although there is literature suggesting that pathophysiologic changes in children with congenital heart disease alter the pharmacokinetics of anesthetics and may result in dosage adjustment, limited information exists regarding the pharmacokinetics of remifentanil in infants with unrepaired tetralogy of Fallot (TOF). The objectives of the current analysis were to characterize the population pharmacokinetics of remifentanil in infants, and to evaluate the effects of TOF on remifentanil's pharmacokinetics.

METHODS

Twenty-seven infants (16 with TOF and 11 with normal cardiac anatomy; aged 114-360 days) scheduled to undergo elective surgery under general anesthesia were recruited in the study. All children received remifentanil 1 μg/kg/min intravenously for anesthesia induction and early maintenance [until ~ 20 min before cardiopulmonary bypass (CPB) for patients with TOF]. Serial arterial blood samples were drawn and analyzed. Population pharmacokinetics of remifentanil was characterized using NONMEM software. The estimates were standardized to a 70-kg adult using a per-kilogram model.

RESULTS

A two-compartment disposition model adequately described the pharmacokinetics of remifentanil. Besides body weight, the introduction of any other covariates, including TOF status, did not improve the model significantly (P > 0.05). The population parameter estimates for systemic clearance (Cl) and inter-compartment clearances (Cl) were 6.03 × (WT/70 kg) and 1.23 × (WT/70 kg) L/min, respectively, and central volume of distribution (V) and peripheral volumes of distribution (V) were 19.6 × (WT/70 kg) and 21.7 × (WT/70 kg) L, respectively.

CONCLUSIONS

Unrepaired TOF does not change the pharmacokinetics of remifentanil, suggesting a similar dosage for infants with TOF compared to normal cardiac anatomy infants.

CLINICAL TRIAL REGISTRATION

The patient enrollment in this study started at 2012, so we do not have clinic trial number, but we still think this is a valuable research and hope it could be considered for publication.

摘要

背景

尽管有文献表明先天性心脏病患儿的病理生理变化会改变麻醉药的药代动力学，可能需要调整剂量，但关于未修复法洛四联症（TOF）婴儿瑞芬太尼药代动力学的信息有限。本分析的目的是描述瑞芬太尼在婴儿中的群体药代动力学，并评估TOF对瑞芬太尼药代动力学的影响。

方法

本研究招募了27名计划在全身麻醉下接受择期手术的婴儿（16名患有TOF，11名心脏解剖结构正常；年龄114 - 360天）。所有儿童静脉输注瑞芬太尼1μg/kg/min用于麻醉诱导和早期维持[TOF患者在体外循环（CPB）前约20分钟停止]。采集并分析系列动脉血样本。使用NONMEM软件描述瑞芬太尼的群体药代动力学。使用每千克模型将估计值标准化为70千克的成年人。

结果

二室处置模型充分描述了瑞芬太尼的药代动力学。除体重外，引入任何其他协变量，包括TOF状态，均未显著改善模型（P>0.05）。全身清除率（Cl）和室间清除率（Cl）的群体参数估计值分别为6.03×（WT/70 kg）和1.23×（WT/70 kg）L/min，中央分布容积（V）和外周分布容积（V）分别为19.6×（WT/70 kg）和21.7×（WT/70 kg）L。