Clinical pharmacogenomics and personalized medicine: New strategies to maximize drug efficacy and avoid adverse drug reaction

Abstract

© Springer Nature Singapore Pte Ltd. 2018. Genetic variability among drug-metabolizing enzymes (DMEs) and transporters influences the pharmacokinetics of the drug and is associated with marked interindividual variability in therapeutic effects and toxicity. Therapeutic drug monitoring (TDM) can facilitate the individualization of dose adjustment of the drug by measuring the plasma concentrations of drug. TDM can be incorporated with the pharmacogenomics, and the metabolic status of the patient can be characterized to optimize the dosage regimen according to the patient's needs. Several polymorphisms among cytochrome P450 (CYP) and phase II enzymes that contribute to the adverse drug reactions (ADRs) have been updated on a regular basis in PharmGKB. A number of pharmacogenomic markers are reported by the Food and Drug Administration and Clinical Pharmacogenetics Implementation Consortium (CPIC) among DMEs for commonly used drugs that are potentially associated with variability in drug response. This review focuses on the genetic polymorphisms of phases I and II DMEs and their associations with drug responses. The drugs discussed in this review requiring a pharmacogenomic test before being prescribed includes efavirenz, voriconazole, clopidogrel, warfarin, tamoxifen, irinotecan, tacrolimus, azathioprine, and risperidone. This chapter also presents the application of pharmacogenomics in the clinic and patient counseling. Finally, a section focuses on the future perspectives of pharmacogenomics and the translation of pharmacogenomic research into routine clinical care.