Influence of age and gender on the pharmacokinetics and pharmacodynamics of remifentanil .1. Model development
Influence of age and gender on the pharmacokinetics and pharmacodynamics of remifentanil .1. Model development
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DOI：
10.1097/00000542-199701000-00004
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发表时间：
1997-01-01
期刊：
影响因子：
8.8
通讯作者：
Shafer, SL
中科院分区：
文献类型：
--
作者：
Minto, CF;Schnider, TW;Shafer, SL
背景资料：以前的研究报道了关于年龄和性别对芬太尼、阿芬太尼和舒芬太尼的药代动力学和药效学影响的相互矛盾的结果。本研究的目的是确定年龄和性别对新的短效阿片类药物remifentanil.Methods的药代动力学和药效学的影响：65名健康成人（38名男性和27名女性）年龄20至85岁，接受1至8 μ g的恒速输注瑞芬太尼。kg（-1）。min（-1），持续4 ~ 20 min。频繁抽取动脉血样本，测定瑞芬太尼浓度。脑电图被用作药物作用的量度。使用软件包NONMEM进行群体药代动力学和药效学建模。使用广义相加模型分析志愿者协变量的影响。简单的表演（无协变量）和复杂在另外15名年龄在41岁至84岁的健康参与者中前瞻性地评估模型（具有协变量）。简单三室药代动力学模型的参数为V-1 = 4.981，V-2 = 9.011，V-3 = 6.541，Cl-1 = 2.46 l/min，Cl-2 = 1.69 l/min，Cl-3 = 0.065 l/min。年龄和瘦体重是显著的协变量。从20岁到85岁，V-1和Cl-1分别下降了约25%和33%。简单S形E（max）药效学模型的参数为k（e0）= 0.516 min（-1），E（0）= 20 Hz，E（max）= 5.62 Hz，EC（50）= 11.2 ng/ml，γ = 2.51。年龄是EC（50）和k（e0）的显著协变量，在研究的年龄范围内均降低约50%。复杂的药代动力学-药效学模型比简单的模型prospectively.Conclusions：本研究确定（1）年龄对瑞芬太尼的药代动力学和药效学的影响;（2）瘦体重对药代动力学参数的影响;（3）性别对任何药代动力学或药效学参数没有影响。
Background: Previous studies have reported conflicting results concerning the influence of age and gender on the pharmacokinetics and pharmacodynamics of fentanyl, alfentanil, and sufentanil. The aim of this study was to determine the influence of age and gender on the pharmacokinetics and pharmacodynamics of the new short-acting opioid remifentanil.Methods: Sixty-five healthy adults (38 men and 27 women) ages 20 to 85 y received remifentanil by constant-rate infusion of 1 to 8 mu g . kg(-1). min(-1) for 4 to 20 min. Frequent arterial blood samples were drawn and assayed for remifentanil concentration. The electroencephalogram was used as a measure of drug effect. Population pharmacokinetic and pharmacodynamic modeling was performed using the software package NONMEM. The influence of volunteer covariates were analyzed using a generalized additive model. The performances of the simple (without covariates) and complex (with covariates) models were evaluated prospectively in an additional 15 healthy participants ages 41 to 84 y.Results: The parameters for the simple three-compartment pharmacokinetic model were V-1 = 4.98 1, V-2 = 9.01 1, V-3 = 6.54 1, Cl-1 = 2.46 l/min, Cl-2 = 1.69 l/min, and Cl-3 = 0.065 l/min. Age and lean body mass were significant covariates. From the ages of 20 to 85 y, V-1 and Cl-1 decreased by approximately 25% and 33%, respectively. The parameters for the simple sigmoid E(max) pharmacodynamic model were k(e0) = 0.516 min(-1), E(0) = 20 Hz, E(max) = 5.62 Hz, EC(50) = 11.2 ng/ml, and gamma = 2.51. Age was a significant covariate of EC(50) and k(e0), with both decreasing by approximately 50% for the age range studied. The complex pharmacokinetic-pharmacodynamic model performed better than did the simple model when applied prospectively.Conclusions: This study identified (1) an effect of age on the pharmacokinetics and pharmacodynamics of remifentanil; (2) an effect of lean body mass on the pharmacokinetic parameters; and (3) no influence of gender on any pharmacokinetic or pharmacodynamic parameter.