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应用支持向量回归预测链脲佐菌素诱导的糖尿病神经病变小鼠模型中药物组合的抗痛觉过敏作用。

The application of support vector regression for prediction of the antiallodynic effect of drug combinations in the mouse model of streptozocin-induced diabetic neuropathy.

机构信息

Faculty of Production Engineering, Warsaw University of Life Sciences, Nowoursynowska 164, 02-787 Warsaw, Poland.

出版信息

Comput Methods Programs Biomed. 2013 Aug;111(2):330-7. doi: 10.1016/j.cmpb.2013.04.018. Epub 2013 May 18.

Abstract

Drug interactions are an important issue of efficacious and safe pharmacotherapy. Although the use of drug combinations carries the potential risk of enhanced toxicity, when carefully introduced it enables to optimize the therapy and achieve pharmacological effects at doses lower than those of single agents. In view of the development of novel analgesic compounds for the neuropathic pain treatment little is known about their influence on the efficacy of currently used analgesic drugs. Below we describe the preliminary evaluation of support vector machine in the regression mode (SVR) application for the prediction of maximal antiallodynic effect of a new derivative of dihydrofuran-2-one (LPP1) used in combination with pregabalin (PGB) in the streptozocin-induced neuropathic pain model in mice. Based on SVR the most effective doses of co-administered LPP1 (4mg/kg) and PGB (1mg/kg) were predicted to cause the paw withdrawal threshold at 6.7g in the von Frey test. In vivo for the same combination of doses the paw withdrawal was observed at 6.5g, which confirms good predictive properties of SVR.

摘要

药物相互作用是有效和安全药物治疗的一个重要问题。虽然药物联合使用有增强毒性的潜在风险,但如果谨慎引入,它可以优化治疗,实现低于单药剂量的药理学效应。鉴于新型镇痛化合物在治疗神经病理性疼痛方面的发展,对于它们对目前使用的镇痛药物疗效的影响知之甚少。下面我们描述了支持向量机回归模式(SVR)在预测新二氢呋喃-2-酮(LPP1)衍生物与普瑞巴林(PGB)联合应用于链脲佐菌素诱导的小鼠神经病理性疼痛模型中最大抗痛觉过敏效应的初步评估中的应用。基于 SVR,预测联合给予 LPP1(4mg/kg)和 PGB(1mg/kg)的最有效剂量在福雷斯特测试中会导致 6.7g 的爪撤回阈值。在体内,对于相同剂量的组合,观察到 6.5g 的爪撤回,这证实了 SVR 的良好预测特性。

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