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Pharmacogenomics drugs metabolism

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https://www.readbyqxmd.com/read/29325731/pharmacogenomic-testing-in-child-and-adolescent-psychiatry-an-evidence-based-review
#1
Anna M Wehry, Laura Ramsey, Shane E Dulemba, Sarah A Mossman, Jeffrey R Strawn
Significant advances have been made in the application of pharmacogenomic testing for the treatment of patients with psychiatric disorders. Over the past decade, a number of studies have evaluated the utility of pharmacogenomic testing in pediatric patients with psychiatric disorders. The evidence base for pharmacogenomic testing in youth with depressive and anxiety disorders as well as attention/deficit hyperactivity disorder (ADHD) is reviewed in this article. General pharmacogenomic principles are summarized and functional polymorphisms in P450 enzymes (and associated metabolizer phenotypes), the serotonin transporter promoter polymorphisms, serotonin 2 A receptor genes (e...
January 8, 2018: Current Problems in Pediatric and Adolescent Health Care
https://www.readbyqxmd.com/read/29313952/how-to-consider-rare-genetic-variants-in-personalized-drug-therapy
#2
Volker M Lauschke, Magnus Ingelman-Sundberg
Personalized drug therapy aims to optimize the efficacy of pharmacological treatments by considering genetic, pathophysiological, dietary, and environmental factors as well as comedications and compliance. A multitude of associations between the specific genetic constitution of the patient and drug pharmacokinetics and pharmacodynamics has been identified in the last decades that encompass mainly common single nucleotide variants (SNVs) and gene copy number variations (CNVs) of importance for the function of genes encoding drug-metabolizing enzymes and transporters involved in drug absorption, distribution, metabolism, and excretion (ADME)...
January 5, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29283396/pharmacogenomics-of-cyp2c9-functional-and-clinical-considerations
#3
REVIEW
Ann K Daly, Allan E Rettie, Douglas M Fowler, John O Miners
CYP2C9 is the most abundant CYP2C subfamily enzyme in human liver and the most important contributor from this subfamily to drug metabolism. Polymorphisms resulting in decreased enzyme activity are common in the CYP2C9 gene and this, combined with narrow therapeutic indices for several key drug substrates, results in some important issues relating to drug safety and efficacy. CYP2C9 substrate selectivity is detailed and, based on crystal structures for the enzyme, we describe how CYP2C9 catalyzes these reactions...
December 28, 2017: Journal of Personalized Medicine
https://www.readbyqxmd.com/read/29283068/influence-of-genetic-polymorphisms-on-mycophenolic-acid-pharmacokinetics-and-patient-outcomes-in-renal-transplantation
#4
Miao Guo, Zi-Jie Wang, Hai-Wei Yang, Ling Meng, Ruo-Yun Tan, Min Gu, Ji-Fu Wei
Mycophenolic acid (MPA) is an immunosuppressive drug widely used in the treatment of organ transplantation and autoimmune diseases. Pharmacokinetics and pharmacodynamics of MPA varies between individuals, the potential reasons being the genetic polymorphisms in key enzymes, drug transporters and target proteins of MPA, involving uridine diphosphate glucuronosyltransferase enzymes, organic anion transport polypeptides, multidrug resistance-associated protein 2, inosine monophosphate dehydrogenase and others...
December 27, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/29261225/in-vitro-validation-of-mirna-mediated-gene-expression-linked-to-drug-metabolism
#5
Botros B Shenoda, Sujay Ramanathan, Seena K Ajit
Pharmacogenomic approaches used to investigate how genes affect drug responses are critical for designing personalized therapies aimed at maximizing efficacy and minimizing adverse effects. Drug efficacy is often dependent on the sequence and expression levels of drug target genes or those involved in the metabolism and transport of the therapeutic agent. Expression of these genes, in turn, is negatively regulated by small noncoding miRNAs. The levels of miRNAs in bodily fluids have been studied extensively as potential diagnostic and prognostic biomarkers...
December 20, 2017: Current Protocols in Pharmacology
https://www.readbyqxmd.com/read/29197117/addition-of-allopurinol-for-altering-thiopurine-metabolism-to-optimize-therapy-in-patients-with-inflammatory-bowel-disease
#6
Geoffrey C Wall, Hamid Muktar, Cassandra Effken, Pramod B Mahajan
Thiopurine drugs, including azathioprine and 6-mercaptopurine, are used commonly in patients with inflammatory bowel disease for maintenance of remission. Although generally well tolerated, adverse effects lead to discontinuation in a significant minority of patients. Pharmacogenomic studies have suggested that metabolic breakdown of azathioprine in an individual is genetically determined. Coupled with the fact that certain thiopurine metabolites, notably 6-thioguanine nucleotide and 6-methylmercaptopurine, are associated with antiinflammatory effects and adverse effects, respectively, some investigators have examined intentionally shunting the metabolism of azathioprine toward increasing 6-thioguanine nucleotide levels by using low doses of the xanthine oxidoreductase inhibitor allopurinol to improve efficacy and decrease toxicity of azathioprine in patients with inflammatory bowel disease...
December 1, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/29192598/personalized-medicine-pharmacogenomic-and-companion-biomarker
#7
Hana Manceau, Kawthar Amrani, Katell Peoc'h
The aim of this review is to provide a brief overview of personalized medicine, pharmacogenetics and companion tests. Personalized or stratified medicine is a new paradigm in the management of patients, aimed at better taking into account inter-individual variability. The response to drugs' intake varies considerably, depending on the transport and metabolism of the drugs, the target and the pathophysiological characteristics of the organism. Each stage is very variable and can be modified by endogenous factors (pathophysiology, age, sex, genetics…) or exogenous (environmental: taking other medicines, food, tobacco, alcohol…)...
December 1, 2017: Annales de Biologie Clinique
https://www.readbyqxmd.com/read/29181807/pharmacogenomic-biomarkers-for-improved-drug-therapy-recent-progress-and-future-developments
#8
Volker M Lauschke, Lili Milani, Magnus Ingelman-Sundberg
Much of the inter-individual variability in drug efficacy and risk of adverse reactions is due to polymorphisms in genes encoding proteins involved in drug pharmacokinetics and pharmacodynamics or immunological responses. Pharmacogenetic research has identified a multitude of gene-drug response associations, which have resulted in genetically guided treatment and dosing decisions to yield a higher success rate of pharmacological treatment. The rapid technological developments for genetic analyses reveal that the number of genetic variants with importance for drug action is much higher than previously thought and that a true personalized prediction of drug response requires attention to millions of rare mutations...
November 27, 2017: AAPS Journal
https://www.readbyqxmd.com/read/29173093/molecular-network-selected-pharmacogenomics-in-a-case-of-bipolar-spectrum-disorder
#9
Stefano Fortinguerra, Alessandro Buriani, Vincenzo Sorrenti, Michele Lenzi, Pietro Giusti
Personal genomic analysis was used for molecular diagnosis and pharmacogenomics in a 53-year-old female suffering from alternating depressive and dysphoric episodes. A total of 52 genes and 108 SNPs were analyzed in the whole genome. Results from the pharmacogenomic analysis were consistent with the pharmacological history and indicate mutations associated with low monoaminergic tone, but also a hyperactive 5HT2A receptor, a feature that associates to a high probability of developing a bipolar condition, especially under 5-hydroxytryptamine potentiating pharmacology...
November 27, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/29160302/role-of-cyp24a1-vdr-and-gc-gene-polymorphisms-on-deferasirox-pharmacokinetics-and-clinical-outcomes
#10
S Allegra, J Cusato, S De Francia, A Arduino, F Longo, E Pirro, D Massano, A De Nicolò, A Piga, A D'Avolio
β-Thalassemia patients develop deficiency in vitamin D absorption and liver hydroxylation, resulting in extremely low calcitriol levels. We explored the role of single-nucleotide polymorphisms (SNPs) involved in vitamin D metabolism, transport and activity on deferasirox pharmacokinetics and outcomes (effectiveness trough levels (Ctrough) and the area under the curve (AUC) cutoffs of 20 μg ml(-1) and 360 μg ml(-1) h(-1), respectively; nonresponse AUC limit of 250 μg ml(-1) h(-1)). Ninety-nine β-thalassemic patients were enrolled...
November 21, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29157489/nmr-based-pharmacometabonomics-a-new-paradigm-for-personalised-or-precision-medicine
#11
REVIEW
Jeremy R Everett
Metabolic profiling by NMR spectroscopy or hyphenated mass spectrometry, known as metabonomics or metabolomics, is an important tool for systems-based approaches in biology and medicine. The experiments are typically done in a diagnostic fashion where changes in metabolite profiles are interpreted as a consequence of an intervention or event; be that a change in diet, the administration of a drug, physical exertion or the onset of a disease. By contrast, pharmacometabonomics takes a prognostic approach to metabolic profiling, in order to predict the effects of drug dosing before it occurs...
November 2017: Progress in Nuclear Magnetic Resonance Spectroscopy
https://www.readbyqxmd.com/read/29099060/clinical-pharmacogenetics-of-cytochrome-p450-associated-drugs-in-children
#12
Ida Aka, Christiana J Bernal, Robert Carroll, Angela Maxwell-Horn, Kazeem A Oshikoya, Sara L Van Driest
Cytochrome P450 (CYP) enzymes are commonly involved in drug metabolism, and genetic variation in the genes encoding CYPs are associated with variable drug response. While genotype-guided therapy has been clinically implemented in adults, these associations are less well established for pediatric patients. In order to understand the frequency of pediatric exposures to drugs with known CYP interactions, we compiled all actionable drug-CYP interactions with a high level of evidence using Clinical Pharmacogenomic Implementation Consortium (CPIC) data and surveyed 10 years of electronic health records (EHR) data for the number of children exposed to CYP-associated drugs...
November 2, 2017: Journal of Personalized Medicine
https://www.readbyqxmd.com/read/29026329/pharmacogenomic-testing-aiding-in-the-management-of-psychotropic-therapy-for-adolescents-with-autism-spectrum-disorders
#13
Seuli Bose-Brill, Jinming Xing, Debra J Barnette, Christopher Hanks
Adolescents with autism have higher rates of anxiety than the general adolescent population. They often struggle to express psychological symptoms verbally where their symptoms may manifest as withdrawal and agitation. Adolescent patients with autism have higher rates of polypharmacy and high-risk psychiatric medication use (eg, atypical antipsychotics) than other patients with psychiatric illness. Primary care pediatricians are at the front lines of psychiatric management for patients with autism. Yet, they have inadequate access to pediatric psychiatry for complex medication management...
2017: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/29022838/pharmacogenomics-of-triazole-antifungal-agents-implications-for-safety-tolerability-and-efficacy
#14
REVIEW
Jarrett R Amsden, Paul O Gubbins
Triazole antifungal agents are prescribed to treat invasive fungal infections in neutropenic and non-neutropenic patients. These antifungal agents are substrates and inhibitors of cytochrome P450 (CYP). Genetic polymorphisms in CYP2C9, CYP2C19 and CYP3A5 can lead to large population-specific variations in drug efficacy and safety, optimal dosing, or contribute to drug interactions associated with this class. Areas covered: This manuscript reviews the pharmacogenomics (i.e. the influence of genetics on drug disposition) of triazole antifungal agents related to their CYP-mediated metabolism and summarizes their implications on triazole efficacy, safety, and tolerability...
November 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28921647/pharmacogenomics-implementation-at-the-national-institutes-of-health-clinical-center
#15
Tristan M Sissung, Jon W McKeeby, Jharana Patel, Juan J Lertora, Parag Kumar, Willy A Flegel, Sharon D Adams, Ellen J Eckes, Frank Mickey, Teri M Plona, Stephanie D Mellot, Ryan N Baugher, Xiaolin Wu, Daniel R Soppet, Mary E Barcus, Vivekananda Datta, Kristen M Pike, Gary DiPatrizio, William D Figg, Barry R Goldspiel
The National Institutes of Health Clinical Center (NIH CC) is the largest hospital in the United States devoted entirely to clinical research, with a highly diverse spectrum of patients. Patient safety and clinical quality are major goals of the hospital, and therapy is often complicated by multiple cotherapies and comorbidities. To this end, we implemented a pharmacogenomics program in 2 phases. In the first phase, we implemented genotyping for HLA-A and HLA-B gene variations with clinical decision support (CDS) for abacavir, carbamazepine, and allopurinol...
October 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28878340/the-pharmacogenomics-of-valproic-acid
#16
REVIEW
Miao-Miao Zhu, Hui-Lan Li, Li-Hong Shi, Xiao-Ping Chen, Jia Luo, Zan-Ling Zhang
Valproic acid is an anticonvulsant and mood-stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder. Adverse effects of valproic acid are rare, but hepatotoxicity is severe in particular in those younger than 2 years old and polytherapy. During valproic acid treatment, it is difficult for prescribers to predict its individual response. Recent advances in the field of pharmacogenomics have indicated variants of candidate genes that affect valproic acid efficacy and safety. In this review, a large number of candidate genes that influence valproic acid pharmacokinetics and pharmacodynamics are discussed, including metabolic enzymes, drug transporters, neurotransmitters and drug targets...
September 7, 2017: Journal of Human Genetics
https://www.readbyqxmd.com/read/28867665/pharmacogenomic-variability-of-oral-baclofen-clearance-and-clinical-response-in-children-with-cerebral-palsy
#17
Matthew J McLaughlin, Yang He, Janice Brunstrom-Hernandez, Liu Lin Thio, Bruce C Carleton, Colin J D Ross, Andrea Gaedigk, Andrew Lewandowski, Hongying Dai, William J Jusko, J Steven Leeder
BACKGROUND: Pharmacogenomic variability can contribute to differences in pharmacokinetics and clinical responses. Pediatric patients with cerebral palsy with genetic variations have not been studied for these potential differences. OBJECTIVE: To determine the genetic sources of variation in oral baclofen clearance and clinical responses. DESIGN: Pharmacogenomic add-on study to determine variability in oral baclofen clearance and clinical responses...
September 1, 2017: PM & R: the Journal of Injury, Function, and Rehabilitation
https://www.readbyqxmd.com/read/28816644/cyp2b6-haplotype-predicts-efavirenz-plasma-concentration-in-black-south-african-hiv-1-infected-children-a-longitudinal-pediatric-pharmacogenomic-study
#18
Riaan Reay, Collet Dandara, Michelle Viljoen, Malie Rheeders
South Africa has the highest burden of the human immunodeficiency virus (HIV) infection globally. Efavirenz (EFV), a frequently used drug against HIV infection, displays a relationship between drug concentration and pharmacodynamics effects clinically. However, haplotype-based genetic variation in drug metabolism in a pediatric sample has been little considered in a longitudinal long-term context. CYP2B6 plays a key role in variation of EFV plasma concentration through altered drug metabolism. We report here on a prospective clinical pharmacogenomics/pharmacokinetic study of Bantu-speaking children, importantly, over a period of 24 months post-initiation of EFV-based treatment in South Africa...
August 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28798474/cyp2c19-2-and-cyp2c19-17-variants-and-effect-of-tamoxifen-on-breast-cancer-recurrence-analysis-of-the-international-tamoxifen-pharmacogenomics-consortium-dataset
#19
Per Damkier, Anders Kjærsgaard, Kimberly A Barker, Deidre Cronin-Fenton, Anatasha Crawford, Ylva Hellberg, Emilius A M Janssen, Carl Langefeld, Thomas P Ahern, Timothy L Lash
The role of cytochrome P450 drug metabolizing enzymes in the efficacy of tamoxifen treatment of breast cancer is subject to substantial interest and controversy. CYP2D6 have been intensively studied, but the role of CYP2C19 is less elucidated, and we studied the association of CYPC19 genotype and recurrence of breast cancer. We used outcome and genotyping data from the large publicly available International Tamoxifen Pharmacogenomics Consortium (ITPC) dataset. Cox regression was used to compute the hazard ratios (HRs) for recurrence...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28771511/exploring-public-genomics-data-for-population-pharmacogenomics
#20
Kleanthi Lakiotaki, Alexandros Kanterakis, Evgenia Kartsaki, Theodora Katsila, George P Patrinos, George Potamias
Racial and ethnic differences in drug responses are now well studied and documented. Pharmacogenomics research seeks to unravel the genetic underpinnings of inter-individual variability with the aim of tailored-made theranostics and therapeutics. Taking into account the differential expression of pharmacogenes coding for key metabolic enzymes and transporters that affect drug pharmacokinetics and pharmacodynamics, we advise that data interpretation and analysis need to occur in light of geographical ancestry, if implications for drug development and global health are to be considered...
2017: PloS One
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