Correspondence between the CYP2C19 and CYP3A4 genotypes with the inferred metabolizer phenotype by omeprazole administration in Mexican healthy children. (7th May 2018)

• Record Type: Journal Article
• Authors: Favela‐Mendoza, A. F.; Martínez‐Cortes, G.; Romero‐Prado, M. M.; Romero‐Tejeda, E. M.; Islas‐Carbajal, M. C.; Sosa‐Macias, M.; Lares‐Asseff, I.; Rangel‐Villalobos, H.
• Is Part Of: Journal of clinical pharmacy and therapeutics. Volume 43:Number 5(2018)
• Page Start: 656
• Page End: 663
• Publication Date: 2018-05-07
• Subjects: children -- CYP2C19 -- CYP3A4 -- metabolizer phenotype -- Mexico -- omeprazole; Clinical pharmacology -- Periodicals; Chemotherapy -- Periodicals; 615
• DOI: 10.1111/jcpt.12699
• Languages: English
• ISSNs: 0269-4727

Abstract

Summary: What is known and objective: CYP2C19 genotypes presumably allow the prediction of the metabolizer phenotypes: poor (PMs), extensive (EMs) and ultra‐rapid (UMs). However, evidence from previous studies regarding this predictive power is unclear, which is important because the benefits expected by healthcare institutions and patients are based on this premise. Therefore, we aimed to complete a formal evaluation of the diagnostic value of CYP2C19 and CYP3A4 genes for predicting metabolizer phenotypes established by omeprazole (OME) administration in 118 healthy children from Jalisco (western Mexico). Methods: The genotypes for CYP3A4*1B and CYP2C19*2, *3, *4, *5 and *17 alleles were determined. CYP2C19 and CYP3A4 phenotypes were obtained after 20 mg OME administration and HPLC quantification in plasma to estimate the Hydroxylation Index (HI = OME/HOME) and Sulfonation Index (SI = OME/SOME), respectively. Results and discussion: The distribution of genotypes and phenotypes for CYP2C19 and CYP3A4 was similar to previous studies in Mexico and Latin America. We estimated the CYP2C19 UM, EM and PM phenotype frequency in 0.84%, 96.61% and 2.54%, respectively. Although differences in the HI distribution were observed between CYP2C19 genotypes, they showed a poor diagnostic ability to predict the CYP2C19 metabolizer phenotype. Similarly, the number of CYP2C19 and CYP3A4 functional alleles was correlated with the HI distribution, but also their diagnostic ability to predict the CYP2C19 phenotype was poor. What is new and conclusion: The CYP2C19 phenotype is not predicted by the number of functional alleles of CYP2C19 and CYP3A4 genes. Phenotyping is still the most valuable alternative to dose individualization for CYP2C19 substrate drugs. Abstract : The number of functional alleles for CYP2C19 and CYP3A4 genes was correlated with the Hydroxylation Index (HI= OME/HOME) and Sulfonation Index (SI= OME/SOME), respectively. Therefore, both CYP2C19 and CYP3A4 genes shape the omeprazole metabolism. However, individually, the number of functional alleles shows poor diagnostic ability to predict the CYP2C19 metabolizer phenotype.