Cyp450 Geno-Phenotype Analysis: Application of Ceiba Cocktail To Mexican Populations

Abstract

e156 Volume 37 Number 8S Extremadura, Badajoz, Spain; Colegio de Ciencias de la Salud, Universidad San Francisco de Quito, Quito, Ecuador; and Servicio de Laboratorio, Hospital de los Valles, Quito, Ecuador Introduction: According to EMA recommendations, development of phenotyping procedures for drug interactions studies and clinical research are highly recommended, due to the discordances found between genotypes determined of the main CYP enzymes and their actual enzymatic activity. Recently, CEIBA cocktail approach to measure metabolic activity of the main CYPs in just one experiment has been designed. However, its optimal design remains to be elucidated, which is the main objective of this research, in order to appropriately select the sample to be analyzed and an optimal single time point for the analysis, to avoid diminish costs and discomfort to the volunteers without compromising the reliability of the results. Material and Methods: Thirteen healthy subjects were given low oral doses of 100mg caffeine, 25mg losartan, 20mg omeprazole and 30 mg dextromethorphan, and blood and urine samples were taken at different time points (predose, 0.5, 1, 2, 3, 4, 6, 8, and 12h) to assay the concentration and pharmacokinetic parameters (AUC). The MRs for CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 were calculated at each time point and their correlation with AUC ratios calculated. All subjects were genotyped. Results: The cocktail was well tolerated and single time point MRs at 4h or 6h (only for CYP2C9) after dosing showed high correlations with corresponding AUC ratios and can, therefore, be proposed as simple phenotyping metrics. On the other hand, metabolic ratios in urine samples were not comparable to plasma ratios. Conclusion: This cocktail was proven to reliably reflect the selected CYPs activities for the evaluation of CYPs hydroxylation capacity. The proposed simplified sampling scheme could facilitate clinical application of CYPs phenotyping with one blood sample collection, in a single analysis. Supported by AEXCID of GOBEX (11IA002) to Sociedad Iberoamericana de Farmacogenetica, Instituto de Salud Carlos IIISara Borrell program (CD13/00348), and Collaboration grant from USFQ (ET); coordinated by the RIBEF network. Disclosure of Interest: None Declared.