Pharmacogenetic Testing: A Tool for Personalized Drug Therapy Optimization

Abstract

Pharmacogenomics is a study of how the genome background is associated with drug resistance and how therapy strategy can be modified for a certain person to achieve benefit. The pharmacogenomics (PGx) testing becomes of great opportunity for physicians to make the proper decision regarding each non-trivial patient that does not respond to therapy. Although pharmacogenomics has become of growing interest to the healthcare market during the past five to ten years the exact mechanisms linking the genetic polymorphisms and observable responses to drug therapy are not always clear. Therefore, the success of PGx testing depends on the physician's ability to understand the obtained results in a standardized way for each particular patient. The review aims to lead the reader through the general conception of PGx and related issues of PGx testing efficiency, personal data security, and health safety at a current clinical level.

Keywords: genetic polymorphism; personalized medicine; pharmacogenetic test; pharmacogenetics.

Figure 1

Genetic variation in metabolic phenotype. Depending on the pharmacogenomics (PGx) testing of genes encoding enzymes that are involved in the drug transport and transformation activity, the examined person can be attributed to either of the defined phenotype (ultra-fast metabolizers (UM), extensive metabolizers (EM), poor metabolism (PM), or intermediate metabolizers (IM)) which, in turn, indicates a personal response to dosage and the certain medication.

Figure 2

Schematic representation of PGx testing steps. Initially, the physician orders the PGx testing to the curated patient. The test is usually performed on saliva or peripheral blood and requires a small amount of biomaterial, and does not require special preparation for the test. After the testing, the physician reviews the obtained report and discuss it with the curated patient to find out whether certain medication can be effective and what is the best dosage for the treatment therapy. The results may also include the prediction of possible side-effect from the prescribed medication.

Figure 3

Samples of PGx test at AyassBioScience: The report is featured with color-coded information for easier navigation and attention. The greed color indicates that the medication can be prescribed according to standard regimens, and the risk for the indicated condition is not increased; yellow color—indicated that dosage adjusting is required, there is an increased vigilance or the patient has a moderate risk for the indicated condition; red color designates that medication has potentially reduced efficacy and increased toxicity or the patient has an increased risk for the indicated condition. In the exemplified results, the patient has a normal response to Apixaban (the drug is a substrate for the efflux transport proteins P-gp (ABCB1) and BCRP (ABCG2) and, possibly, decreased response to Bupropion. Bupropion is metabolized to its active metabolite hydroxybupropion by CYP2B6. This metabolite contributes to the therapeutic effects of bupropion when used as a smoking cessation agent or as an antidepressant. The patient has also increased response to Codeine, which is converted into its active metabolite morphine by CYP2D6. Since this patient is the ultra-rapid metabolizer (UM), a greatly increased morphine level is expected, and the patient is at high risk of toxicity when taking codeine.