Asymptotics of the total net direct pharmacological effect for large drug doses.
Asymptotics of the total net direct pharmacological effect for large drug doses.
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大药物剂量的总净直接药理作用的渐近。
DOI：
10.1007/s002850000052
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Krzyzanski,W
中科院分区：
文献类型：
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作者：
Krzyzanski,W
直接药理作用E由E与药物血浆浓度cp的emax模型描述。效果与时间曲线下面积（AUCE）被用作总净药理学效应的测量。药物血浆浓度是常微分方程的室室系统的解，输入在有限时间后终止，并由单个剂量样参数按比例控制。导出了大剂量cpp的时间导数的渐近性，并将其用作必须由函数满足的条件，该函数的积分定义的渐近性已导出。这与药物浓度保持在阈值水平以上的时间成正比。阈值dec50表示引起最大效应50%的药物血浆浓度。对于大剂量，参数tc > ec50与药物剂量的对数成正比，当剂量增加到无穷大时，其渐近性计算到o(1)阶。结果适用于基本药代动力学系统。
The direct pharmacological effect E is described by theEmaxmodel relating E to the drug plasma concentrationCp. The area under the effect vs. time curve (AUCE) is used as the measurement of the total net pharmacological effect. The drug plasma concentrations are solutions of compartmental systems of ordinary differential equations with the input terminated after a finite time and controlled in a proportional manner by a single dose-like parameter. The asymptotics of the time derivative ofCpfor large doses are derived and used as conditions which have to be satisfied by functions for which the asymptotics of the integral definingAUCEare derived. TheAUCEis proportional to the timeTC>EC50for which the drug concentration stays above the threshold levelEC50. The thresholdEC50denotes the drug plasma concentration which elicits 50% of the maximum effect. The parameterTC>EC50is proportional to the logarithm of drug dose for large doses and its asymptotics is calculated up to the order o(1) as dose increases to infinity. The results are applied to basic pharmacokinetic systems.