Abstract
As targeted personalized therapy becomes more widely used in human medicine, clients will expect the veterinary clinician to be able to implement an evidence-based strategy regarding both the prescribing of medicines and also recognition of the potential for adverse drug reactions (ADR) for their pet, at breed and individual level. This review aims to provide an overview of current developments and challenges in pharmacogenetics in medicine for a veterinary audience and to map these to developments in veterinary pharmacogenetics. Pharmacogenetics has been in development over the past 100 years but has been revolutionized following the publication of the human, and then veterinary species genomes. Genetic biomarkers called pharmacogenes have been identified as specific genetic loci on chromosomes which are associated with either positive or adverse drug responses. Pharmacogene variation may be classified according to the associated drug response, such as a change in (1) the pharmacokinetics; (2) the pharmacodynamics; (3) genes in the downstream pathway of the drug or (4) the effect of “off-target” genes resulting in a response that is unrelated to the intended target. There are many barriers to translation of pharmacogenetic information to the clinic, however, in human medicine, international initiatives are promising real change in the delivery of personalized medicine by 2025. We argue that for effective translation into the veterinary clinic, clinicians, international experts, and stakeholders must collaborate to ensure quality assurance and genetic test validation so that animals may also benefit from this genomics revolution.
Highlights
Pharmacogenetics has been defined in human medicine as the “variability due to hereditary” [1] and as such, the concept pre-dates the discoveries of the Human Genome project
This review aims to provide an overview of the current developments and challenges in PGx in medicine for a veterinary audience, to map to and expand on these with respect to current PGx knowledge and potential developments in veterinary pharmacotherapeutics
PGx variances may be classified into groupings based on the drug response “differences” which impact on drug metabolism, efficacy, and risk of adverse effects
Summary
Pharmacogenetics has been defined in human medicine as the “variability due to hereditary” [1] and as such, the concept pre-dates the discoveries of the Human Genome project. The term “pharmacogenomics” initially was used to describe the development of new drugs based on new understanding provided by genomic research, and the terms “pharmacogenetics” and “pharmacogenomics” are often used interchangeably [1], “pharmacogenomics” is considered to focus on the “expressed genome” and techniques to study drug responses include proteomics, RRH: Translating PGx to the Clinic metabolomics, and gene expression [2] To encompass both concepts, the abbreviation PGx has come into use, defined as “the individualization of drug therapy through medication selection or dose adjustment based upon direct (e.g., genotyping) or indirect (e.g., phenotyping) assessment of an individual’s genetic constitution for drug response” Swen et al [3]. This review aims to provide an overview of the current developments and challenges in PGx in medicine for a veterinary audience, to map to and expand on these with respect to current PGx knowledge and potential developments in veterinary pharmacotherapeutics
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