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

Department of Pharmacology, Medicine School, University of Zaragoza, Domingo Miral s/n, 50009 Zaragoza, Spainbsinues{at}posta.unizar.es

Ana Fanlo

Mara Luisa Bernal

Marta Val

Esteban Mayayo

Department of Pharmacology, Medical School, University of Zaragoza, Zaragoza, Spain

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 theCYP2C19*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 micro nuclei 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.

Key Words: CYP2C19 • CYP1A2 • genotoxicity • omeprazole

Human & Experimental Toxicology, Vol. 23, No. 3, 107-113 (2004)
DOI: 10.1191/0960327104ht431oa


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