Undevia Samir D, Gomez-Abuin Gonzalo, Ratain Mark J
Cancer Research Center, The University of Chicago, 5841 South Maryland Avenue, MC 2115 Chicago, Illinois 60637, USA.
Nat Rev Cancer. 2005 Jun;5(6):447-58. doi: 10.1038/nrc1629.
The translation of advances in cancer biology to drug discovery can be complicated by pharmacokinetic variation between individuals and within individuals, and this can result in unpredictable toxicity and variable antineoplastic effects. Previously unrecognized variables (such as genetic polymorphisms) are now known to have a significant impact on drug disposition. How can the pharmacokinetic variability of anticancer agents be reduced? This will require the understanding of correlations between pharmacokinetics and treatment outcomes, the identification of relevant patient parameters, mathematical modelling of individual and population pharmacokinetics, and the development of algorithms that will tailor doses to the individual patient.
癌症生物学进展转化为药物研发可能会因个体间和个体内的药代动力学差异而变得复杂,这可能导致不可预测的毒性和抗肿瘤效果的差异。以前未被认识的变量(如基因多态性)现在已知对药物处置有重大影响。如何降低抗癌药物的药代动力学变异性?这将需要理解药代动力学与治疗结果之间的相关性,识别相关的患者参数,对个体和群体药代动力学进行数学建模,以及开发能为个体患者量身定制剂量的算法。