Drug metabolism genotypes and their association with adverse drug reactions in selected populations: a pilot study of methodology

Aims - (1) To undertake a pilot population study of the investigation of ph armacogenetic factors that may lead to adverse drug reactions (ADRs). (2) T o investigate whether a population of patients taking fluoxetine, moclobemi de or omeprazole reported to the New Zealand (NZ) Intensive Medicines Monit oring Programme (IMMP) with ADRs, have a higher frequency of CYP2D6 and CYP 2C19 poor metabolizer (PM) genotypes than a reference population. (3) To de termine the frequency of CYP2C19 alleles in the NZ Caucasian population. Methods - 150 patients who had been notified to the NZ IMMP as experiencing an adverse event after being prescribed fluoxetine, moclobemide or omepraz ole (50 on each) were approached by letter and asked if they would consent to take part. Of these, 31 patients and 56 subjects from a population of bl ood donors were genotyped for common CYP2D6 and CYP2C19 alleles. Results and conclusions - At either loci the distributions of genotypes wer e not significantly different in the IMMP patients compared with the refere nce population or with other reported studies. In this small study CYP2D6 o r CYP2C19 PM genotypes are not overrepresented in selected patients with ad verse reactions. Population studies involving sampling of blood for genotyp ing are feasible in the general population. Copyright (C) 2000 John Wiley & Sons, Ltd.