Response surface model for anesthetic drug interactions
Response surface model for anesthetic drug interactions
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DOI：
10.1097/00000542-200006000-00017
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发表时间：
2000-06-01
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
工作背景：麻醉药物相互作用传统上采用等效线分析或多元逻辑回归来表征，这两种方法都有明显的局限性。作者提出了一个基于响应面法的模型。该模型可以表征麻醉药物组合之间的整个剂量-反应关系，并且在数学上与单一药物的浓度-反应关系模型一致。方法：作者定义了一个参数，θ，描述了两种潜在相互作用药物的浓度比。本文对经典的sigmoid E-max模型进行了扩展，使模型参数依赖于θ，并根据已有的数据，用计算机程序估计了咪达唑仑、丙泊酚和阿芬太尼之间催眠相互作用的响应面，模拟了最大协同剂量组合后效应的预测时程。根据试验数据，每种配对组合均显示出显著的协同作用。基于效应部位相互作用的计算机模拟预测，与单独使用异丙酚相比，最大协同作用的三种药物组合使效应持续时间增加了两倍。结论：响应面可以描述麻醉相互作用，甚至是激动剂、部分激动剂、竞争性拮抗剂和反激动剂之间的相互作用。应用响应面方法可以表征完整的浓度-响应关系，因此可以用于制定最佳药物剂量的实用指南。
Background: Anesthetic drug interactions traditionally have been characterized using isobolographic analysis or multiple logistic regression, Both approaches have significant limitations. The authors propose a model based on response-surface methodology. This model can characterize the entire dose-response relation between combinations of anesthetic drugs and is mathematically consistent with models of the concentration-response relation of single drugs.Methods: The authors defined a parameter, theta, that describes the concentration ratio of two potentially interacting drugs. The classic sigmoid E-max model was extended by making the model parameters dependent on theta, A computer program was used to estimate response surfaces for the hypnotic interaction between midazolam, propofol, and alfentanil, based on previously published data, The predicted time course of effect was simulated after maximally synergistic bolus dose combinations.Results: The parameters of the response surface were identifiable. With the test data, each of the paired combinations showed significant synergy. Computer simulations based on interactions at the effect site predicted that the maximally synergistic three-drug combination tripled the duration of effect compared with propofol alone.Conclusions: Response surfaces can describe anesthetic interactions, even those between agonists, partial agonists, competitive antagonists, and inverse agonists. Application of response-surface methodology permits characterization of the full concentration-response relation and therefore can be used to develop practical guidelines for optimal drug dosing.