de Andrés Fernando, Sosa-Macías Martha, Lazalde-Ramos Blanca P, Naranjo María Eugenia G, Tarazona-Santos Eduardo, Llerena Adrián
Drug Metabol Drug Interact. 2013;28(3):135-46. doi: 10.1515/dmdi-2013-0020.
Interindividual differences in response to drug treatments are mainly caused by differences in drug metabolism, in which cytochrome P450 (CYP450) enzymes are involved. Genetic polymorphisms of these enzymes have a key role in this variability. However, environmental factors, endogenous metabolism and disease states also have a great influence on the actual drug metabolism rate (metabolic phenotype). Consequently, the genotype does not always correlate with the actual drug hydroxylation phenotype. In this sense, in vivo phenotyping strategies represent an alternative to evaluate the interindividual variability in drug metabolism. Therefore, the 'cocktail' approach is considered as an advantageous strategy to obtain actual and reliable information on several CYP activities in just one experiment. As reviewed, phenotyping studies on Latin-American populations, which comprise about 400 million people, are scarce, and only selective phenotyping methods were applied. Therefore, a novel cocktail approach is here proposed as a phenotyping tool to evaluate the relationship between genotype and phenotype of major CYP enzymes in Hispanic populations. This determination will allow adaptation of drug therapies to these populations and consequently to benefit from the application of pharmacogenetics in the reduction of drug adverse effects and in the improvement of therapeutic responses.
个体对药物治疗反应的差异主要由药物代谢差异引起，细胞色素P450（CYP450）酶参与其中。这些酶的基因多态性在这种变异性中起关键作用。然而，环境因素、内源性代谢和疾病状态也对实际药物代谢率（代谢表型）有很大影响。因此，基因型并不总是与实际药物羟化表型相关。从这个意义上说，体内表型分析策略是评估药物代谢个体间变异性的一种替代方法。因此，“鸡尾酒”方法被认为是一种有利的策略，只需一次实验就能获得关于几种CYP活性的实际且可靠的信息。如综述所述，对约4亿人口的拉丁裔人群的表型分析研究很少，且仅应用了选择性表型分析方法。因此，本文提出一种新的“鸡尾酒”方法作为表型分析工具，以评估西班牙裔人群中主要CYP酶的基因型与表型之间的关系。这一测定将使药物治疗能够适应这些人群，从而受益于药物遗传学在减少药物不良反应和改善治疗反应方面的应用。
