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 pharmacogenetic factors that may lead to adverse drug reactions (ADRs). (2) To investigate whether a population of patients taking fluoxetine, moclobemide or omeprazole reported to the New Zealand (NZ) Intensive Medicines Monitoring Programme (IMMP) with ADRs, have a higher frequency of CYP2D6 and CYP2C19 poor metabolizer (PM) genotypes than a reference population. (3) To determine 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 omeprazole (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 blood donors were genotyped for common CYP2D6 and CYP2C19 alleles.Results and conclusions-At either loci the distributions of genotypes were not significantly different in the IMMP patients compared with the reference population or with other reported studies. In this small study CYP2D6 or CYP2C19 PM genotypes are not overrepresented in selected patients with adverse reactions. Population studies involving sampling of blood for genotyping are feasible in the general population. Copyright (c) 2000 John Wiley & Sons, Ltd.
Clark
D
D
Department of Pharmacology, School of Medical Sciences, University of Otago, Dunedin, New Zealand.
Morgan
A
A
Hananeia
L
L
Coulter
D
D
Olds
R
R