Evaluation of drug-metabolizing enzyme hydroxylation phenotypes in Hispanic populations: the CEIBA cocktail

Abstract

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.

Population pharmacogenetics and global health

“…Thirteen articles have been published so far that focus on population studies, including an article from the RIBEF-CEIBA Consortium, which is a population pharmacogenetics initiative from the Iberian-Latinoamerican Pharmacogenetic Network RIBEF [3]. The FDA and the EMA support studies on pharmacogenetics and ethnicity.…”

Can the CEIBA Cocktail Designed for Human Cytochrome P450 Enzymes be Used in the Rat for Drug Interaction Studies?

“…Nowadays it is consensual that a great part of interindividual variability in drug response is related to differences in the capacity of drugmetabolizing enzymes, especially the cytochrome P450 (CYP) isoenzymes (1)(2)(3)(4). Although the differences in drug metabolism capacity is greatly determined by genetic polymorphisms, additional intrinsic and extrinsic factors are able to modulate CYPs activity, contributing thus to the actual drug metabolic phenotype (3)(4)(5).…”

“…Recently, we proposed the CEIBA cocktail consisting of four probe drugs [caffeine (CAF), omeprazole (OZ), dextromethorphan (DM) and losartan (LOS)] for the simultaneous phenotyping of the five major human drug-metabolizing CYP isoenzymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4) in just one assay (3,4,25). Nonetheless, its potential application in the rat has never been studied.…”

A tribute to José María ("Chema") Cantú

“…An example of one such collaboration initiative fostered by Chema Cantú was the Ibero-Latin-American Network of Pharmacogenetics and Pharmacogenomics, RIBEF (de Andrés et al , 2012; Llerena et al , 2013), in which one of us (ALL) collaborated closely with Chema in congregating geneticists and pharmacologists from Spain and most Latin American countries in a network with the objectives of training and technology transfer in pharmacogenomics and the creation of databases of population studies of diseases and drugs in the participating countries. The performance of the network has been extremely successful, having yielded published pharmacogenetic studies of Mexican, Cuban, Nicaraguan, Ecuadorean and Spanish populations (de Andrés et al , 2012; Llerena et al , 2013) and a number of forthcoming publications on genetic polymorphisms most relevant for drug metabolism. These studies have been the basis for a number of doctoral and master theses of trainees in many countries in Latin America.…”