Pharmacogenetics in clinical practice: Challenges and opportunities

Abstract

Pharmacogenetics studies the influence of genetic variation on drug response, while pharmacogenomics is a genome-wide and multifactorial extension of the term pharmacogenetics. Both pharmacogenetics and pharmacogenomics are the backbones of the concept called personalized medicine. Although a "personalized" approach has always been a goal of good medical practice, there is a new aspect of the extensive use of molecular data to tailor drug therapy to an individual patient, in order to maximize therapeutic benefit and minimize adverse events. The main causes of inter-individual variability in a patient are genetic variations in genes responsible for enzymes synthesis, which participate in absorption, distribution, metabolism and excretion (ADME system) of drugs. So, all patients can be classified in four groups, according to their genotype: slow metabolizers, intermediate metabolizers, ul-trafast metabolizers and extensive metabolizers who are most frequent and are considered to be a standard group of patients. The group of most essential metabolism enzymes is represented by a superfamily of cytochrome P450 (CYP2D6, CYP2C9, CYP2C19, etc.). Enzymes from this family contribute to inter-individual differences in drug concentration in the plasma. The effects of polymorphisms in the CYP P450, range from an ineffective drug therapy to severe toxicity it can cause (e.g. drugs with a narrow therapeutic range (e.g., Warfarin) in patients with a reduced activity of CYP P450). Pharmacogenetic testing is carried out for a number of reasons: for selecting patients most likely to achieve therapeutic efficacy, in order to reduce side effects and determine the most appropriate dose, in order to achieve efficiency and a higher degree of therapy safety. The advantage of pharmacogenetic testing is reflected in the fact that it can be applied prior to drug application. Pharmacogenetics should satisfy patients' need for an effective therapy without side effects, physicians' need for assistance in selecting an adequate remedy and dosage for a particular patient, as well as other health care professionals, government agencies and pharmacists' needs.