Crivori P, Poggesi I
Prediction and Modeling, Nerviano Medical Sciences Srl, Nerviano Medical Sciences Srl, Italy.
Eur J Med Chem. 2006 Jul;41(7):795-808. doi: 10.1016/j.ejmech.2006.03.003. Epub 2006 Apr 27.
The site of biotransformation, the extent and rate of metabolism and the number of active metabolic pathways are among the most important characteristics of the pharmacokinetics of a drug. The catalytic activity of drug metabolizing enzymes is likely the most influential determinant of the pharmacokinetic variability. Metabolic stability is the prerequisite for sustaining the therapeutically relevant concentrations. Metabolic inhibition and induction can give rise to clinically important drug-drug interactions. A variety of computational approaches are currently available for predicting different cytochrome P450 (CYP)-related metabolism endpoints. The present review will describe these approaches and their impact on drug development process. Indications on the available software for the implementation will also be given.
生物转化部位、代谢程度和速率以及活性代谢途径的数量是药物药代动力学最重要的特征之一。药物代谢酶的催化活性可能是药代动力学变异性最具影响力的决定因素。代谢稳定性是维持治疗相关浓度的前提条件。代谢抑制和诱导可引发具有临床重要性的药物相互作用。目前有多种计算方法可用于预测不同的细胞色素P450（CYP）相关代谢终点。本综述将描述这些方法及其对药物研发过程的影响。还将给出关于可用实施软件的说明。
