使用体重依赖异速生长指数建立小儿患者瑞芬太尼的人群药代动力学模型。

Carl-Michael Staschen, Iftekhar Mahmood
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引用次数: 14

摘要

背景:异速生长指数在人群药代动力学分析中经常被使用,但异速生长指数的固定或估计问题仍然存在争议。当前分析的目的是评估瑞芬太尼的体重依赖异速生长指数(BDE)模型的性能。方法:对34例新生儿~ 17岁,体重2.5 ~ 97 kg的患者进行单次静脉输注瑞芬太尼(5 μg/kg)的研究。采用群体药代动力学方法,通过以下BDE方程描述药物清除率:CL=CLpop(BW/14.6 kg)L×BW(-M)。采用三种异速生长模型探讨异速生长指数对瑞芬太尼总清除率的影响。结果:所有模型拟合的结构、协变量和统计参数的估计精度(%RSE)良好至优异。然而,根据计算的赤池权值(模型1为0.000,模型2为0.004,模型3为0.996),模型3是描述个体间隙估计最稳健的模型。结论:BDE模型对瑞芬太尼清除率的估计效果最好,符合实际,具有实用价值。这些模型有待进一步研究。
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A population pharmacokinetic model of remifentanil in pediatric patients using body-weight-dependent allometric exponents.

Background: Allometric exponents in population pharmacokinetic analysis are regularly used but the issue of fixing or estimating an allometric exponent remains controversial. The objective of the current analysis is to evaluate the performance of a body-weight-dependent allometric exponent (BDE) model of remifentanil.

Methods: The study was conducted in 34 patients (neonates to 17 years and 2.5 to 97 kg body weight) following a single intravenous (IV) infusion of remifentanil (5 μg/kg). A population pharmacokinetic approach was taken to describe drug clearance by the following BDE equation: CL=CLpop(BW/14.6 kg)L×BW(-M). Three allometric models were used to explore the impact of allometric exponents on the total clearance of remifentanil.

Results: All model-fitted structural, covariate, and statistical parameters were estimated with good to excellent precision (%RSE). However, on the basis of calculated Akaike weights (0.000 for model 1, 0.004 for model 2, and 0.996 for model 3), model 3 is the most robust model to describe individual clearance estimates.

Conclusions: The BDE model performed best for the estimation of remifentanil clearance and is realistic and of practical value. Further investigation should be conducted for such models.

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