The role of drug metabolizing enzymes in personalized therapy

Abstract

Individual differences in drug response, both beneficial and adverse, has long been recognized as complex and common problem in clinical practice (Ramamoorthy et al., 2015). Pharmacogenetics (PGx) aims at identifying genes and genetic variants that affect the clinical outcome of therapy, i.e. determination of inherited genetic differences and genetic mechanisms that condition or disposition efficacy and toxicity of drugs (Jones 2013). PGx prediction of the therapeutic outcome in each patient individually, is a challenge and it’s usage in clinical practice is still far from reality. The extensive research efforts undertaken over the past decade have identified several genetic markers that are strongly associated with outcomes of interest. Appraising the drug related function of CYP450 (CYP2D6, CYP2C9, CYP2C19, CYP3A5 and AKR1D1) genetic variants is the core for efficient modeling of population specific, cost-effective, PGx platform for individualization of drug therapy (Cabaleiro et al., 2015; Holmes et al., 2011; Jiang et al., 2015; Kapedanovska Nestorovska et al., 2014; López-Rodríguez et al., 2008; Patel et al., 2014; Rejon-Parrilla et al., 2014) . The objective of this study is to determine the differential expression of polymorphic CYP450 genes and the correlation of mRNA levels in the liver and peripheral blood, to evaluate the clinical validity of the CYP450 phenotype in prediction of pharmacokinetic properties and therapeutic outcome of substrate drugs (CYP2D6 for risperidone, CYP2C19 for clopidogrel and CYP2C9 for ibuprofen) and to assess cost-effectiveness of PGx platform for individualized treatment with risperidone and clopidogrel in our country.