Pharmacogenetics: From Bench to Byte

Abstract

Despite initial enthusiasm, the use of pharmacogenetics has remained limited to investigation in only a few clinical fields such as oncology and psychiatry. The main reason is the paucity of scientific evidence to show that pharmacogenetic testing leads to improved clinical outcomes. Moreover, for most pharmacogenetic tests (such as tests for genetic variants of cytochrome P450 enzymes) a detailed knowledge of pharmacology is a prerequisite for application in clinical practice, and both physicians and pharmacists might find it difficult to interpret the clinical value of pharmacogenetic test results. Guidelines that link the result of a pharmacogenetic test to therapeutic recommendations might help to overcome these problems, but such guidelines are only sparsely available. In 2001, an early step was taken to develop such guidelines for the therapeutic use of antidepressants, and these included CYP2D6-related dose recommendations drawn from pharmacokinetic study data. However, the use of such recommendations in routine clinical practice remains difficult, because they are currently outside the ambit of the clinical environment and are not accessible during the decision-making process by physicians and pharmacists, namely the prescription and dispensing of drugs.

Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine

“…The CPIC [9] and DPWG [10,11] publish guidelines, whose primary focus is to provide guidance on the use of genetic information to guide prescribing practices, should these genetic information become available. Currently, DPWG provide dose recommendations for four out of six PPIs: omeprazole, esomeperazole, pantoprazole, and lansoprazole.…”

“…As of February 2017, CPIC has published 21 sets of guidelines for 35 drugs, spanning a wide range of medical areas, including cardiovascular, cancer, pain, immunosuppressants, antidepressants, anti-infective agents and others. Similar efforts to advance the field are also led by the Royal Dutch Pharmacogenetics Working Group (DPWG) [10,11], and the Ubiquitous Pharmacogenomics Consortium to integrate pharmacogenetics into clinic care across multiple countries in Europe [12]. …”

Iterative Development and Evaluation of a Pharmacogenomic-Guided Clinical Decision Support System for Warfarin Dosing

“…The variability in warfarin response is partially due to genetic differences in the cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) [15]. Pharmacogenomic tests may help clinicians manage warfarin more effectively and minimize the risk of serious bleeding [16,17]. In August 2007, the United States FDA approved a change in warfarin labeling to incorporate information related to how CYP2C9 and VKORC1 genetic variability can impact appropriate warfarin dosing and response [18].…”

“…Interface quality (items [16][17][18] * all questions on the CSUQ use 1=Strongly Agree, 2=Agree, 3=Somewhat Agree, 4=Neither Agree nor Disagree, 5=Somewhat Disagree, 6=Disagree, and 7=Strongly Disagree. …”

“…An important setback is the fact that there are conflicting reports regarding the effectiveness of incorporating genetic testing into warfarin dosing [21,22]. The aforementioned barrier in the complexity of the genetic output also presents clinical challenges given the large amount of data [17,19,23]. While less complex pharmacogenomics-guided CDSSs have been implemented, more complex genetic and clinical factors need further refinement.…”