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Pharmacogenomics Oct 2004Methotrexate (MTX) has proven efficient in the treatment of a number of malignancies, as well as non-malignant disorders characterized by a rapid cellular growth. Yet... (Review)
Review
Methotrexate (MTX) has proven efficient in the treatment of a number of malignancies, as well as non-malignant disorders characterized by a rapid cellular growth. Yet some patients might develop resistance, while others could have toxic side effects. MTX achieves its cytotoxicity through the inhibition of folate-dependent enzymes, suggesting that the genes controlling their activity or the levels of folate cofactors can modulate drug efficacy and, thus, the sensitivity of a patient to MTX. Indeed, several studies, conducted mostly in leukemia and rheumatoid arthritis patients, have addressed the potential for tailoring MTX therapy based on a patient's genetics. Several genetic variants have been shown to have a predictive role, among which the most frequently studied are those of methylenetetrahydrofolate reductase and thymidylate synthase genes. The other candidates, as well as gene-gene interactions, which may be even more important for the prediction of disease outcomes than the individual gene effects, are also briefly discussed.
Topics: Animals; Humans; Methotrexate; Pharmacogenetics
PubMed: 15469405
DOI: 10.1517/14622416.5.7.819 -
Healthcare Management Forum May 2020The use of pharmacogenetic information is becoming mainstream with insurance companies and others starting to pay for widescale implementation of this new technology...
The use of pharmacogenetic information is becoming mainstream with insurance companies and others starting to pay for widescale implementation of this new technology starting with patients who have anxiety and depression. It has been introduced in response to the unpredictability of medication, the high number of adverse drug events, and lack of drug effectiveness. Greater than one-third of patients are identified as having one or more pharmacogenetic variants. Each pharmacogenetic variant may affect the metabolism of several medications used in primary care, in addition to the antidepressant and anti-anxiolytic medications. Pharmacogenetic information is evolving with major international working groups providing continuous updates. It is challenging to incorporate this new information along with all the other variables needed to identify safe and effective drug options within a normal consultation. Medication decision support software is one solution that can help address this.
Topics: Cost-Benefit Analysis; Evidence-Based Medicine; Pharmacogenetics; Primary Health Care
PubMed: 32054324
DOI: 10.1177/0840470419901285 -
Expert Opinion on Drug Metabolism &... Sep 2019: Over the last decade, the spread of next-generation sequencing technology along with the rising cost in health management in national health systems has led to... (Review)
Review
: Over the last decade, the spread of next-generation sequencing technology along with the rising cost in health management in national health systems has led to widespread use/abuse of pharmacogenetic tests (PGx) in the practice of many clinical disciplines. However, given their clinical significance, it is important to standardize these tests for having an interaction with the clinical analysis laboratory (CAL), in which a PGx service can meet these requirements. : A diagnostic test must meet the criteria of reproducibility and validity for its utility in the clinical routine. This present review mainly describes the utility of introducing PGx tests in the CAL routine to produce correct results useful for setting up personalized drug treatments. : With a PGx service, CALs can provide the right tool to help clinicians to make better choices about different categories of drugs and their dosage and to manage the economic impact both in hospital-based settings and in National Health Services, throughout electronic health records. Advances in PGx also allow a new approach for pharmaceutical companies in order to improve drug development and clinical trials. As a result, CALs can achieve a powerful source of epidemiological, clinical, and research findings from PGx tests.
Topics: Animals; Dose-Response Relationship, Drug; Drug Development; Drug Industry; High-Throughput Nucleotide Sequencing; Humans; Pharmaceutical Preparations; Pharmacogenetics; Pharmacogenomic Testing; Precision Medicine; Reproducibility of Results
PubMed: 31512953
DOI: 10.1080/17425255.2019.1658742 -
Gastroenterology Jul 2003Many drugs exhibit variable efficacy and toxicity. Pharmacogenetics explores the genetic underpinnings of variable drug response. Pharmacogenetic testing is beginning to... (Review)
Review
Many drugs exhibit variable efficacy and toxicity. Pharmacogenetics explores the genetic underpinnings of variable drug response. Pharmacogenetic testing is beginning to enter the clinic and will have a significant impact on the practice of clinical gastroenterology. Thiopurine S-methyltransferase screening, which will likely become routine for thiopurine recipients, illustrates the promise and limitations of pharmacogenetics. Testing for variation in other drug metabolism pathways may also become important. Pharmacogenetics will complement but not replace traditional methods for choosing drugs and for selecting dosing regimens for narrow-therapeutic-index drugs.
Topics: Gastroenterology; Gastrointestinal Agents; Gastrointestinal Diseases; Humans; Pharmacogenetics
PubMed: 12851888
DOI: 10.1016/s0016-5085(03)00683-8 -
Drug Metabolism Reviews Oct 2004Pharmacogenetics, one of the fields of clinical pharmacology, studies how genetic factors influence drug response. If hereditary traits are taken into account... (Review)
Review
Pharmacogenetics, one of the fields of clinical pharmacology, studies how genetic factors influence drug response. If hereditary traits are taken into account appropriately before starting drug treatment, the type of drug and its dosage can be tailored to the individual patient's needs. Pharmacogenetics adds a considerable amount of stringency to the doctor's therapeutic approach. Today, it is the relationship between dosage requirements and genetic variations in drug metabolizing enzymes like cytochrome P450 (CYP) 2D6 and CYP2C19, or in drug transporters like p-glycoprotein, that is substantiated best. A standard dose will bring about more adverse effects than usual if enzymatic activity is lacking or feeble. Sometimes, however, therapeutic response might be better due to higher concentrations: proton pump inhibitors for eradication of Helicobacter pylori are more efficacious in carriers of a deficient CYP2C19 variant. The drug's interaction with its target (e.g. receptor) also depends on genetic factors. In some cases genetic tests can help distinguish between responders and non-responders of a specific drug treatment. The first pharmacogenetic tests are already on the market.
Topics: Animals; Cytochrome P-450 Enzyme System; Genetic Variation; Humans; Pharmaceutical Preparations; Pharmacogenetics; Polymorphism, Single Nucleotide; Xenobiotics
PubMed: 15554239
DOI: 10.1081/dmr-200033458 -
Current Protocols in Human Genetics Jan 2009Pharmacogenetics is the study of relationships between genetic variation and inter-individual differences with respect to drug response. As the field has matured over... (Review)
Review
Pharmacogenetics is the study of relationships between genetic variation and inter-individual differences with respect to drug response. As the field has matured over the past 15 years, a remarkable diversity of pathways, variation types, and mechanisms have been found to be relevant pharmacogenetic factors. Today, pharmacogenetics is becoming more important in pharmacology for target validation, lead optimization, and understanding of idiosyncratic toxicity. This unit provides an overview of the history of pharmacogenetics and current research applications in drug discovery, as well as a discussion of research quality issues relevant for human subjects research in the pharmacogenetics laboratory.
Topics: Animals; Base Sequence; Drug Design; Genetic Variation; Humans; Models, Genetic; Molecular Sequence Data; Pharmacogenetics
PubMed: 19170034
DOI: 10.1002/0471142905.hg0919s60 -
Current Protocols in Human Genetics May 2006Pharmacogenetics is the study of relationships between genetic variation and inter-individual differences with respect to drug response. As the field has matured over... (Review)
Review
Pharmacogenetics is the study of relationships between genetic variation and inter-individual differences with respect to drug response. As the field has matured over the past 15 years, a remarkable diversity of pathways, variation types, and mechanisms have been found to be relevant pharmacogenetic factors. Today, pharmacogenetics is becoming more important in pharmacology for target validation, lead optimization, and understanding of idiosyncratic toxicity. This unit provides an overview of the history of pharmacogenetics and current research applications in drug discovery, as well as a discussion of research quality issues relevant for human subjects research in the pharmacogenetics laboratory.
Topics: Animals; Drug Delivery Systems; Enzymes; Gene Expression Regulation; Humans; Pharmaceutical Preparations; Pharmacogenetics
PubMed: 18428399
DOI: 10.1002/0471142905.hg0919s49 -
Cold Spring Harbor Perspectives in... Feb 2019Inherited genetic variations in pharmacogenetic loci are widely acknowledged as important determinants of phenotypic differences in drug response, and may be actionable... (Review)
Review
Inherited genetic variations in pharmacogenetic loci are widely acknowledged as important determinants of phenotypic differences in drug response, and may be actionable in the clinic. However, recent studies suggest that a considerable number of novel rare variants in pharmacogenes likely contribute to a still unexplained fraction of the observed interindividual variability. Next-generation sequencing (NGS) represents a rapid, relatively inexpensive, large-scale DNA sequencing technology with potential relevance as a comprehensive pharmacogenetic genotyping platform to identify genetic variation related to drug therapy. However, many obstacles remain before the clinical use of NGS-based test results, including technical challenges, functional interpretation, and strict requirements for diagnostic tests. Advanced computational analyses, high-throughput screening methodologies, and generation of shared resources with cell-based and clinical information will facilitate the integration of NGS data into candidate genotyping approaches, likely enhancing future drug phenotype predictions in patients.
Topics: Computational Biology; Genetic Variation; High-Throughput Nucleotide Sequencing; High-Throughput Screening Assays; Humans; Pharmacogenetics; Phenotype; Sequence Analysis, DNA
PubMed: 29844222
DOI: 10.1101/cshperspect.a033027 -
The Pharmacogenomics Journal 2004Bipolar disorder (BD) is a major psychiatric condition that commonly requires prophylactic and episodic treatment. There is important variability in the therapeutic... (Review)
Review
Bipolar disorder (BD) is a major psychiatric condition that commonly requires prophylactic and episodic treatment. There is important variability in the therapeutic response and side-effect profiles to currently available pharmacological agents. Pharmacogenetics have provided new hopes to develop more efficient treatment strategies tailored to the individual patient's needs. This review assesses nonsystematically studies using pharmacogenetic strategies in BD. Most of these studies have focused on patients selected according to lithium response, and more recently, a growing number of studies have been investigating genetic factors in mixed samples of patients classified according to response to antidepressant treatment. Although previous clinical and family studies support the use of pharmacogenetic strategies both to increase phenotype homogeneity as well as to identify genetic factors that may mediate response to treatment, most molecular studies carried out to date are still preliminary and in need of external validation. A major problem has been comparability between studies, in part, because of differences in the criteria used to define response. More attention should be paid to standardize the criteria for drug response definition.
Topics: Antidepressive Agents; Bipolar Disorder; Humans; Pharmacogenetics
PubMed: 15079146
DOI: 10.1038/sj.tpj.6500245 -
Pharmacy World & Science : PWS Jun 2006This commentary draws attention to and raises awareness of forthcoming pharmacogenetic technologies amongst the pharmacy profession. It aims to stimulate debate around... (Review)
Review
This commentary draws attention to and raises awareness of forthcoming pharmacogenetic technologies amongst the pharmacy profession. It aims to stimulate debate around the potential role that the pharmacy profession can play in the introduction of pharmacogenetic technologies into primary healthcare. This commentary discusses potential new roles for pharmacists involving pharmacogenetic technologies, giving attention to the way the profession may need to adapt to accommodate these.
Topics: Education, Pharmacy; Evidence-Based Medicine; Humans; Pharmacists; Pharmacogenetics; Pharmacy
PubMed: 17004018
DOI: 10.1007/s11096-006-9029-3