Omeprazole treatment: genotoxicity biomarkers, and potential to induce CYP1A2 activity in humans.

Blanca Sinués, Ana Fanlo, Maria Luisa Bernal, Marta Val, Esteban Mayayo

Journal: Human & experimental toxicology 2004;23(3):107-13

PMID: 15119530

Abstract

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.

Address: Department of Pharmacology, Medical School, University of Zaragoza, Zaragoza, Spain. [email protected]

DOI: 10.1191/0960327104ht431oa

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MeSH Terms: Adolescent, Adult, Anti-Ulcer Agents, Aryl Hydrocarbon Hydroxylases, Caffeine, Cell Division, Chromosome Aberrations, Cytochrome P-450 CYP1A2, Cytochrome P-450 CYP2C19, Enzyme Induction, Female, Genotype, Humans, Male, Micronuclei, Chromosome-Defective, Middle Aged, Mitotic Index, Mixed Function Oxygenases, Mutagens, Omeprazole, Sister Chromatid Exchange