文章：

抗癌药物的药代动力学变异性

Pharmacokinetic variability of anticancer agents

原文发布日期：2005-06-01

DOI: 10.1038/nrc1629

类型: Review Article

开放获取: 否

要点：

1. The field of pharmacokinetics attempts to describe the bodily disposition of drugs in terms of numerical parameters that are calculated from plasma concentrations obtained at time points after drug administration. These parameters can be correlated with treatment outcomes such as toxicity and efficacy.
2. Anticancer drugs can have considerable interindividual pharmacokinetic variability, which, given the narrow therapeutic index of these drugs, results in unpredictable clinical effects.
3. There are many potential sources of pharmacokinetic variation, including interindividual differences in absorption, distribution, metabolism and excretion of anticancer drugs.
4. A considerable amount of research is currently directed towards defining genetic polymorphisms in drug-disposition pathways that explain observed interindividual pharmacokinetic variability.
5. Tailoring doses of anticancer drug to the individual patient will decrease interpatient pharmacokinetic variability and reduce the risks of severe toxicity and subtherapeutic treatment.
6. Individualized dosing strategies currently being examined in the research setting are promising, although few are used in routine clinical practice.

要点翻译：

1. 药代动力学领域试图根据给药后不同时间点测得的血浆浓度计算出的数值参数，来描述药物在体内的处置过程。这些参数可与毒性、疗效等治疗结果相关联。
2. 抗癌药物存在显著的个体间药代动力学差异，加之这类药物治疗窗狭窄，导致其临床效应难以预测。
3. 药代动力学变异的潜在来源众多，包括个体间在抗癌药物吸收、分布、代谢和排泄方面存在的差异。
4. 当前大量研究致力于阐明药物处置通路中的基因多态性，以期解释观察到的个体间药代动力学差异。
5. 根据患者个体情况调整抗癌药物剂量将减少患者间的药代动力学变异，降低严重毒性和疗效不足的风险。
6. 虽然目前鲜有个体化给药策略应用于常规临床实践，但研究领域正在探索的个体化给药方案展现出广阔前景。

英文摘要：

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.

摘要翻译： 

将癌症生物学的进展转化为药物发现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可变的抗肿瘤效果。以前未被认识到的变量（如遗传多态性）现在已知对药物处置有显著影响。如何减少抗癌药物的药代动力学变异性？这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，以及开发能够为个体患者量身定制剂量的算法。

原文链接：

Pharmacokinetic variability of anticancer agents