Relevance of CYP2D6-1584C>G polymorphism for thioridazine:mesoridazine plasma concentration ratio in psychiatric patients

Aims: The CYP2D6 -1584C>G (rs1080985) polymorphism has been identified as another major factor for CYP2D6 function that is possibly associated with ultrarapid metabolism. The mutant -1584G promoter genotype seems to be consistently related to a higher protein expression than -1584C. However, the impact this SNP in the CYP2D6 promoter region has on plasma levels of patients taking CYP2D6 substrates, such as thioridazine, has not been studied. Previously, we showed the validity of the mesoridazine:thioridazine ratio to assess CYP2D6 activity in clinical settings. Therefore, the aim of this study was to analyze the relationship between the presence of the CYP2D6 -1584C>G polymorphism and the plasma concentrations of thioridazine and its metabolites in a previously studied population of patients in order to evaluate the implications for CYP2D6 hydroxylation capacity. Materials & methods: The CYP2D6 -1584C>G polymorphism was determined by using a PCR-RFLP method in 61 Caucasian psychiatric patients receiving t...