CYP2C19- and CYP3A4-dependent omeprazole metabolism in West Mexicans

• Published in: Journal of clinical pharmacology Vol. 43; no. 11; p. 1211
• Main Authors: Gonzalez, Héctor M, Romero, Elba M, Peregrina, A Aaron, de J Chávez, Teresa, Escobar-Islas, Estanislao, Lozano, Felipe, Hoyo-Vadillo, Carlos
• Format: Journal Article
• Language: English
• Published: England 01.11.2003
• Subjects: Adolescent; Adult; Analysis of Variance; Aryl Hydrocarbon Hydroxylases - genetics; Aryl Hydrocarbon Hydroxylases - metabolism; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System - genetics; Cytochrome P-450 Enzyme System - metabolism; Female; Humans; Male; Mexico; Mixed Function Oxygenases - genetics; Mixed Function Oxygenases - metabolism; Omeprazole - metabolism; Phenotype; Polymorphism, Genetic - genetics
• ISSN: 0091-2700
• DOI: 10.1177/0091270003258170

Omeprazole has been used as a drug probe for CYP2C19, but no systematic data are available for Mexican populations. The aim of this study was to evaluate the phenotype frequencies of the CYP2C19 polymorphism in West Mexicans. Besides omeprazole, sulfone was measured to evaluate CYP3A4 after administration of the 20-mg dose to 127 healthy volunteers. Logarithms of metabolic indexes of omeprazole/hydroxyomeprazole for CYP2C19 and omeprazole/omeprazole sulfone for CYP3A4 had trimodal distributions. Five subjects (4%) had a log CYP2C19 metabolic index below -0.9, suggesting an ultra-extensive phenotype. Poor metabolizers (log metabolic index > 0.6) were 6%. For CYP3A4, 11 subjects (9%) were below -0.3 of the log metabolic index. The log metabolic index of omeprazole/omeprazole sulfone was above the antimode of 0.6 for 11% of this population. The mean log metabolic index of CYP3A4 extensive metabolizers (80%) was 0.166, which seems to be higher than the data described for Caucasians and lower than that for Asians.