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Pharmacogenomics Apr 2020Tacrolimus is the gold standard immunosuppressant administered in solid organ and stem cell transplantation to avoid graft rejection post-transplant. Despite its... (Review)
Review
Tacrolimus is the gold standard immunosuppressant administered in solid organ and stem cell transplantation to avoid graft rejection post-transplant. Despite its widespread use, there is a large variation in response to therapy, likely due to high inter-individual pharmacokinetic variability. Therapeutic drug monitoring is employed to improve clinical response and reduce toxicity. There is substantial evidence that pharmacogenetics influences drug exposure and response. genotype significantly impacts oral tacrolimus concentrations and response after solid organ transplantation. There are fewer studies in stem cell transplantation and with intravenous tacrolimus dosing. This report highlights recent evidence suggesting genes such as and play a larger role after intravenous dosing compared with , and the role for novel genes on tacrolimus outcomes.
Topics: Drug Administration Routes; Humans; Immunosuppressive Agents; Pharmacogenetics; Stem Cell Transplantation; Tacrolimus
PubMed: 32308133
DOI: 10.2217/pgs-2019-0189 -
The Pharmacogenomics Journal Oct 2017Pharmacogenetics (PGx) has the potential to personalize pharmaceutical treatments. Many relevant gene-drug associations have been discovered, but PGx-guided treatment... (Review)
Review
Pharmacogenetics (PGx) has the potential to personalize pharmaceutical treatments. Many relevant gene-drug associations have been discovered, but PGx-guided treatment needs to be cost-effective as well as clinically beneficial to be incorporated into standard health-care. We reviewed economic evaluations for PGx associations listed in the US Food and Drug Administration (FDA) Table of Pharmacogenomic Biomarkers in Drug Labeling. We determined the proportion of evaluations that found PGx-guided treatment to be cost-effective or dominant over the alternative strategies, and estimated the impact on this proportion of removing the cost of genetic testing. Of the 137 PGx associations in the FDA table, 44 economic evaluations, relating to 10 drugs, were identified. Of these evaluations, 57% drew conclusions in favour of PGx testing, of which 30% were cost-effective and 27% were dominant (cost-saving). If genetic information was freely available, 75% of economic evaluations would support PGx-guided treatment, of which 25% would be cost-effective and 50% would be dominant. Thus, PGx-guided treatment can be a cost-effective and even a cost-saving strategy. Having genetic information readily available in the clinical health record is a realistic future prospect, and would make more genetic tests economically worthwhile.
Topics: Cost-Benefit Analysis; Economics, Pharmaceutical; Pharmacogenetics; Pharmacogenomic Testing; Precision Medicine; United States; United States Food and Drug Administration
PubMed: 28607506
DOI: 10.1038/tpj.2017.21 -
Animal Genetics Feb 2024The recent advances in high-throughput next-generation sequencing technologies have heralded the arrival of the Big Data era. As a result, the use of pharmacogenetics in... (Review)
Review
The recent advances in high-throughput next-generation sequencing technologies have heralded the arrival of the Big Data era. As a result, the use of pharmacogenetics in drug discovery and individualized drug therapy has transformed the field of precision medicine. This paradigm shift in drug development programs has effectively reshaped the old drug development practices, which were primarily concerned with the physiological status of patients for drug development. Pharmacogenomics bridges the gap between pharmacodynamics and pharmacokinetics, advancing current diagnostic and treatment strategies and enabling personalized and targeted drug therapy. The primary goals of pharmacogenetic studies are to improve drug efficacy and minimize toxicities, to identify novel drug targets, to estimate drug dosage for personalized medicine, and to incorporate it as a routine diagnostic for disease susceptibility. Although pharmacogenetics has numerous applications in individualized drug therapy and drug development, it is in its infancy in veterinary medicine. The objective of this review is to present an overview of historical landmarks, current developments in various animal species, challenges and future perspectives of genomics in drug development and dosage optimization for individualized medicine in veterinary subjects.
Topics: Animals; Pharmacogenetics; Precision Medicine; Genomics; High-Throughput Nucleotide Sequencing
PubMed: 37990577
DOI: 10.1111/age.13376 -
Biomedicine & Pharmacotherapy =... Jun 2022Mendelian randomization (MR) is an epidemiological method that uses genetic variants to proxy an exposure predicting its causal association with an outcome. It occupies... (Review)
Review
Mendelian randomization (MR) is an epidemiological method that uses genetic variants to proxy an exposure predicting its causal association with an outcome. It occupies a valuable niche between observational studies and randomized trials. MR applications expanded lately, facilitated by the availability of big data, to include disease risk causation prediction, supporting evidence of prior observational data, identifying new drug targets, and drug repurposing. Concurrently, the last decade witnessed the growth of pharmacogenomics (PGx) research as a cornerstone in precision medicine. PGx research, conducted at discovery and implementation levels, resulted in validated PGx biomarkers and tests. Despite many clinically relevant PGx associations that could be translated into clinical applications, worldwide implementation is lagging far behind. The current review examines the intersection zones between MR and PGx research. MR can provide supporting evidence that allows generalizing PGx findings supporting its implementation. Interchangeability, PGx research can fuel MR studies with libraries of genetic variants of validated biological relevance. Furthermore, PGx and MR exhibit a synergistic relationship in drug discovery that can accelerate identifying new targets and repurposing old drugs. Interdisciplinary research applied by PGx researchers, epidemiologists with MR experience, and data scientists' collaborations can unlock unforeseen opportunities in accelerating precision medicine acquisition.
Topics: Drug Discovery; Mendelian Randomization Analysis; Pharmacogenetics; Precision Medicine
PubMed: 35429744
DOI: 10.1016/j.biopha.2022.112952 -
Methods in Molecular Biology (Clifton,... 2023Genetic variants can alter response to drugs and other therapeutic interventions. The study of this phenomenon, called pharmacogenomics, is similar in many ways to other...
Genetic variants can alter response to drugs and other therapeutic interventions. The study of this phenomenon, called pharmacogenomics, is similar in many ways to other types of genetic studies but has distinct methodological and statistical considerations. Genetic variants involved in the processing of exogenous compounds exhibit great diversity and complexity, and the phenotypes studied in pharmacogenomics are also more complex than typical genetic studies. In this chapter, we review basic concepts in pharmacogenomic study designs, data generation techniques, statistical analysis approaches, and commonly used methods and briefly discuss the ultimate translation of findings to clinical care.
Topics: Pharmacogenetics; Pharmacogenomic Testing; Phenotype; Research Design
PubMed: 36929083
DOI: 10.1007/978-1-0716-2986-4_14 -
American Journal of Health-system... Dec 2016The operational elements essential for establishing an inpatient pharmacogenetic service are reviewed, and the role of the pharmacist in the provision of genotype-guided... (Review)
Review
PURPOSE
The operational elements essential for establishing an inpatient pharmacogenetic service are reviewed, and the role of the pharmacist in the provision of genotype-guided drug therapy in pharmacogenetics programs at three institutions is highlighted.
SUMMARY
Pharmacists are well positioned to assume important roles in facilitating the clinical use of genetic information to optimize drug therapy given their expertise in clinical pharmacology and therapeutics. Pharmacists have assumed important roles in implementing inpatient pharmacogenetics programs. This includes programs designed to incorporate genetic test results to optimize antiplatelet drug selection after percutaneous coronary intervention and personalize warfarin dosing. Pharmacist involvement occurs on many levels, including championing and leading pharmacogenetics implementation efforts, establishing clinical processes to support genotype-guided therapy, assisting the clinical staff with interpreting genetic test results and applying them to prescribing decisions, and educating other healthcare providers and patients on genomic medicine. The three inpatient pharmacogenetics programs described use reactive versus preemptive genotyping, the most feasible approach under the current third-party payment structure. All three sites also follow Clinical Pharmacogenetics Implementation Consortium guidelines for drug therapy recommendations based on genetic test results.
CONCLUSION
With the clinical emergence of pharmacogenetics into the inpatient setting, it is important that pharmacists caring for hospitalized patients are well prepared to serve as experts in interpreting and applying genetic test results to guide drug therapy decisions. Since genetic test results may not be available until after patient discharge, pharmacists practicing in the ambulatory care setting should also be prepared to assist with genotype-guided drug therapy as part of transitions in care.
Topics: Genotype; Hospitalization; Humans; Patient Care Team; Pharmacogenetics; Pharmacy Service, Hospital; Professional Role; Program Development
PubMed: 27864202
DOI: 10.2146/ajhp150946 -
Revue Neurologique 2015Pharmacogenetics aims to identify the underlying genetic factors participating in the variability of drug response. Indeed, genetic variability at the DNA or RNA levels... (Review)
Review
INTRODUCTION
Pharmacogenetics aims to identify the underlying genetic factors participating in the variability of drug response. Indeed, genetic variability at the DNA or RNA levels can directly or indirectly modify the pharmacokinetic or the pharmacodynamic parameters of a drug. The ultimate aim of pharmacogenetics is to move towards a personalised medicine by predicting responders and non-responders, adjusting the dose of the treatment, and identifying individuals at risk of adverse drug effects.
METHODS
A literature research was performed in which we reviewed all pharmacogenetic studies in neurological disorders including neurodegenerative diseases, multiple sclerosis, stroke and epilepsy.
RESULTS
Several pharmacogenetic studies have been performed in neurology, bringing insights into the inter-individual drug response variability and in the pathophysiology of neurological diseases. The principal implications of these studies for the management of patients in clinical practice are discussed.
CONCLUSION/DISCUSSION
Although several genetic factors have been identified in the modification of drug response in neurological disorders, most of them have a marginal predictive effect at the single gene level, suggesting mutagenic interactions as well as other factors related to drug interaction and disease subtypes. Most pharmacogenetic studies deserve further replication in independent populations and, ideally, in pharmacogenetic clinical trials to demonstrate their relevance in clinical practice.
Topics: Heredodegenerative Disorders, Nervous System; Humans; Nervous System Diseases; Pharmacogenetics
PubMed: 26008819
DOI: 10.1016/j.neurol.2015.04.003 -
Genes Oct 2020Digital health (DH) is the use of digital technologies and data analytics to understand health-related behaviors and enhance personalized clinical care. DH is... (Review)
Review
Digital health (DH) is the use of digital technologies and data analytics to understand health-related behaviors and enhance personalized clinical care. DH is increasingly being used in clinical trials, and an important field that could potentially benefit from incorporating DH into trial design is pharmacogenetics. Prospective pharmacogenetic trials typically compare a standard care arm to a pharmacogenetic-guided therapeutic arm. These trials often require large sample sizes, are challenging to recruit into, lack patient diversity, and can have complicated workflows to deliver therapeutic interventions to both investigators and patients. Importantly, the use of DH technologies could mitigate these challenges and improve pharmacogenetic trial design and operation. Some DH use cases include (1) automatic electronic health record-based patient screening and recruitment; (2) interactive websites for participant engagement; (3) home- and tele-health visits for patient convenience (e.g., samples for lab tests, physical exams, medication administration); (4) healthcare apps to collect patient-reported outcomes, adverse events and concomitant medications, and to deliver therapeutic information to patients; and (5) wearable devices to collect vital signs, electrocardiograms, sleep quality, and other discrete clinical variables. Given that pharmacogenetic trials are inherently challenging to conduct, future pharmacogenetic utility studies should consider implementing DH technologies and trial methodologies into their design and operation.
Topics: Computational Biology; Humans; Medical Informatics; Pattern Recognition, Automated; Pharmacogenetics; Pharmacogenomic Testing; Precision Medicine; Telemedicine; Wearable Electronic Devices
PubMed: 33114567
DOI: 10.3390/genes11111261 -
Genes Sep 2021This narrative review aims to provide an overview of the main Machine Learning (ML) techniques and their applications in pharmacogenetics (such as antidepressant,... (Review)
Review
This narrative review aims to provide an overview of the main Machine Learning (ML) techniques and their applications in pharmacogenetics (such as antidepressant, anti-cancer and warfarin drugs) over the past 10 years. ML deals with the study, the design and the development of algorithms that give computers capability to learn without being explicitly programmed. ML is a sub-field of artificial intelligence, and to date, it has demonstrated satisfactory performance on a wide range of tasks in biomedicine. According to the final goal, ML can be defined as Supervised (SML) or as Unsupervised (UML). SML techniques are applied when prediction is the focus of the research. On the other hand, UML techniques are used when the outcome is not known, and the goal of the research is unveiling the underlying structure of the data. The increasing use of sophisticated ML algorithms will likely be instrumental in improving knowledge in pharmacogenetics.
Topics: Computational Biology; Machine Learning; Pharmacogenetics
PubMed: 34680905
DOI: 10.3390/genes12101511 -
Journal of Neural Transmission (Vienna,... Jan 2019
Topics: Humans; Mental Disorders; Pharmacogenetics; Psychiatry
PubMed: 30673860
DOI: 10.1007/s00702-018-01968-9