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基于转运蛋白的代谢性数字肝生理模型(digital liver model,DLM)程序由VBA(visual basic aplication)编辑而成,整合了代谢酶、转运蛋白多态性信息及动物生理学参数和中国人口统计学数据,依据离体或在体的药代动力学实验结果模拟预测候选药物在动物及中国人肝脏内的代谢清除过程,估算药物清除率及药物相互作用。本文应用该模型模拟预测了普伐他汀、匹伐他汀的清除率及与环孢素的相互作用。83.3%(5/6)同一种属内参数预测平均值在文献值的2倍范围内,且能够很好地预测药物在临床上的相互作用趋势,对指明试验方向、降低临床试验风险有重要意义。
The transporter-based metabolic digital liver model (DLM) program, edited by VBA (visual basic aplication), incorporates metabolic enzyme, transporter polymorphism information and animal physiology parameters and Chinese demographic data The drug clearance rate and drug interactions were estimated based on the ex vivo or in vivo pharmacokinetic test results to predict the metabolic clearance of candidate drugs in the liver of animals and Chinese. The model was applied to predict the clearance of pravastatin and pitavastatin and its interaction with cyclosporine. 83.3% (5/6) The average prediction value of the same species in the literature is within 2 times the literature value, and can predict the trend of clinical drug interactions well, which is important for pointing out the test direction and reducing the risk of clinical trial significance.