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CYP2C19- and CYP3A4-Dependent Omeprazole Metabolism in West Mexicans

From CUCEI, Universidad de Guadalajara, Mexico (Mr. Gonzalez, Ms. Romero T., Mr. Peregrina L., Ms. de J. Chávez C.); Division of Pharmacology, Cinvestav, IPN, Mexico (Mr. Escobar-Islas, Dr. Hoyo-Vadillo); and Hospital General de Zona #14, IMSS, Mexico (Dr. Lozano K.).

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.

Key Words: Omeprazole • CYP2C19 • CYP3A4 • pharmacogenetics • Mexicans • genetic polymorphisms

Address for reprints: Dr. Carlos Hoyo-Vadillo, Division of Pharmacology, Cinvestav, IPN, Av IPN 2508, 07360 Mexico DF, Mexico.

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