Cytochrome P450 2D6 (CYP2D6) genotyping on postmortem blood as a supplementary tool for interpretation of forensic toxicological results

Debrisoquine hydroxylase (CYP2D6) is involved in the metabolism of many tox icologically important drugs. The gene encoding for this enzyme displays a polymorphic distribution in all populations examined. We report a study on 46 cases, where analyses of the CYP2D6 gene were conducted on postmortem fe moral blood in order to investigate the occurrence of poor metabolizers (PM ). A polymerase chain reaction (PCR) method, designed and routinely used fo r therapeutic drug monitoring, was employed, only slightly modified. Sample s from 22 cases, where the parent drug to metabolite ratio was unexpectedly high were analyzed as well as samples from 24 control cases. Genotyping co uld be carried out in all but one case. Previous freezing or addition of po tassium fluoride as preservative did not prevent analysis. Only one PM (fro m the control group) was discovered, implying an occurrence of only 2.2% as compared to the reported frequency of approx. 7% in Sweden. Among the exte nsive metabolizers (EM), however, a number of individuals with mutated gene s were identified. Although it seems reasonable to suspect a PM genotype in cases with a high concentration of a drug metabolized by CYP2D6, but witho ut suspicion of acute overdose, our study does not support the opinion that this interpretation pitfall is particularly common. This study rather indi cates that drug interactions in EMs constitute a more frequent and importan t problem. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.