ULTRARAPID DRUG-METABOLISM - PCR-BASED DETECTION OF CYP2D6 GENE DUPLICATION

The enzyme debrisoquine 4-hydroxylase (CYP2D6), which metabolizes many widely used drugs, is highly polymorphic. The activity of the enzyme ranges between subjects from ultrafast to a complete absence. Therefor e, metabolic capacity varies, producing intersubject differences in th erapeutic efficacy and side effects at standard recommended doses. Up to 7% of Caucasians may demonstrate ultrarapid drug metabolism (UM) be cause of inherited alleles with multiplicate functional CYP2D6 genes, causing an increased amount of enzyme to be expressed. Identification of UM subjects is of potential clinical importance for adjustment of d oses in drug therapy, as well as to avoid misidentification of noncomp liance. In our study, we tested recently designed PCR assays for the d etection of the UM genotype. We found a 3.5% prevalence of UMs carryin g duplicate active CYP2D6 genes in a population consisting of 202 psyc hiatric patients.