Omeprazole treatment: genotoxicity biomarkers, and potential to induce CYP1A2 activity in humans.
Omeprazole is one of the most used acid-suppressing medications. This fact emphasizes the questions concerning the safety of this compound. Healthy volunteers (n=33) were included in this prospective study. All study subjects were analysed for their CYP2C19 genotype. Of the 33 individuals, 24 were homozygous for the wild type CYP2C19*1 allele, 7 were heterozygous for the CYP2C19*2 variant allele, and 2 were homozygous for the CYP2C19*2 variant allele. Before and after 14 days of omeprazole treatment at a daily dose of 20 mg, one blood sample was taken from each individual to determine five cytogenetic biomarkers of genotoxicity: chromosome aberrations, micronuclei, proliferating rate index, sister chromatid exchanges, and mitotic index. The only significant change was that of a weak increase in micronuclei count after treatment in relation to baseline values (day 0) (P = 0.026). To assess the potential of omeprazole to induce P450 CYP1A2, the urinary ratio AFMU+1X+1U/17U in the interval of 4-5 hours after caffeine intake was calculated twice (days 0 and 15), using the caffeine test in 27 of the 33 individuals. This result suggests that omeprazole does not increase CYP1A2 activity after 14 days of treatment.
Sinués
Blanca
B
Department of Pharmacology, Medical School, University of Zaragoza, Zaragoza, Spain. bsinues@posta.unizar.es
Fanlo
Ana
A
Bernal
Maria Luisa
ML
Val
Marta
M
Mayayo
Esteban
E
D000293:Adolescent; D000328:Adult; D000897:Anti-Ulcer Agents / Q000009:adverse effects / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D002110:Caffeine / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002869:Chromosome Aberrations / Q000139:chemically induced; D019388:Cytochrome P-450 CYP1A2 / Q000096:biosynthesis* / Q000187:drug effects; D065731:Cytochrome P-450 CYP2C19; D004790:Enzyme Induction; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects; D008875:Middle Aged; D008940:Mitotic Index; D006899:Mixed Function Oxygenases / Q000235:genetics / Q000378:metabolism; D009153:Mutagens; D009853:Omeprazole / Q000009:adverse effects / Q000494:pharmacology*; D012854:Sister Chromatid Exchange / Q000187:drug effects
D000897:Anti-Ulcer Agents; D009153:Mutagens; D002110:Caffeine; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D019388:Cytochrome P-450 CYP1A2; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole