CYP2C19- and CYP3A4-dependent omeprazole metabolism in West Mexicans.
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.
Gonzalez
Héctor M
HM
CUCEI, Universidad de Guadalajara, Mexico.
Romero
Elba M
EM
Peregrina
A Aaron
AA
de J Chávez
Teresa
T
Escobar-Islas
Estanislao
E
Lozano
Felipe
F
Hoyo-Vadillo
Carlos
C
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism*; D065731:Cytochrome P-450 CYP2C19; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008800:Mexico; D006899:Mixed Function Oxygenases / Q000235:genetics / Q000378:metabolism*; D009853:Omeprazole / Q000378:metabolism*; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics
D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; C104464:CYP3A protein, human; D065731:Cytochrome P-450 CYP2C19; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D009853:Omeprazole