COMPARISON OF 4 BASIC MODELS OF INDIRECT PHARMACODYNAMIC RESPONSES
COMPARISON OF 4 BASIC MODELS OF INDIRECT PHARMACODYNAMIC RESPONSES
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DOI：
10.1007/bf01061691
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发表时间：
1993-08-01
期刊：
影响因子：
--
通讯作者：
JUSKO, WJ
中科院分区：
文献类型：
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作者：
DAYNEKA, NL;GARG, V;JUSKO, WJ
已经开发并比较了表征给药后间接药效学反应的四种基本模型。这些模型是基于药物对控制药物反应的输入或消散的因素的影响（抑制或刺激）。甲基强的松龙的药代动力学参数用于使用计算机模拟生成血浆浓度和响应时间曲线。结果发现，所产生的反应显示出缓慢的开始和缓慢的恢复到基线。最大反应时间与模型和剂量有关。在每种情况下，滞后曲线显示药物浓度先于响应。当响应与基于分布到假设效应室的药效学模型拟合时，所得参数具有剂量依赖性，并推断生物学不可信性。间接反应模型必须区别于传统的药效学模型，后者假设药物的直接作用。四种基本间接反应模型的假设、方程和数据模式为评价药理学效应提供了起点，其中作用部位先于或跟随测量的反应变量。
Four basic models for characterizing indirect pharmacodynamic responses after drug administration have been developed and compared. The models are based on drug effects (inhibition or stimulation) on the factors controlling either the input or the dissipation of drug response. Pharmacokinetic parameters of methylprednisolone were used to generate plasma concentration and response-time profiles using computer simulations. It was found that the responses produced showed a slow onset and a slow return to baseline. The time of maximal response was dependent on the model and dose. In each case, hysteresis plots showed that drug concentrations preceded the response. When the responses ware fitted with pharmacodynamic models based on distribution to a hypothetical effect compartment, the resulting parameters were dose-dependent and inferred biological implausibility. Indirect response models must be treated as distinct from conventional pharmacodynamic models which assume direct action of drugs. The assumptions, equations, and data patterns for the four basic indirect response models provide a starting point for evaluation of pharmacologic effects where the site of action precedes or follows the measured response variable.