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Pharmacogenomics drugs metabolism

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https://www.readbyqxmd.com/read/29792895/pharmacogenomics-of-drug-induced-liver-injury-dili-molecular-biology-to-clinical-applications
#1
REVIEW
Kalaiyarasi Kaliyaperumal, Jane I Grove, Robin M Delahay, William J H Griffiths, Adam Duckworth, Guruprasad P Aithal
A number of drug-specific and host-related factors contribute to the development of drug-induced liver injury (DILI). Investigations focused on genetic susceptibility to DILI have advanced our understanding of the pathogenesis of this rare, yet potentially life-threatening adverse reaction. Candidate gene studies involving well-characterized patients with DILI and drug-exposed controls have identified single nucleotide polymorphisms (SNPs) affecting the metabolism and clearance of specific drugs and hence, influencing individual's susceptibility to DILI...
May 21, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29709540/implications-of-pharmacogenomics-to-the-management-of-ibs
#2
REVIEW
Michael Camilleri
The objectives are to review the role of pharmacogenomics in drug metabolism of medications typically used in patients with irritable bowel syndrome (IBS) focusing predominantly on cytochrome P450 metabolism. Other aims are to provide examples of genetic variation of receptors or intermediary pathways that are targets for IBS drugs and to critically appraise the situations where precision medicine is impacting health in IBS. Pharmacogenomics impacts both pharmacokinetics and pharmacodynamics. Although large clinical trials have not incorporated testing for genetic variations that could impact the efficacy of medications in IBS, there are therapeutic advantages to inclusion of pharmacogenomics testing for individual patients, as has been demonstrated particularly in the treatment with central neuromodulators in psychiatry practice...
April 27, 2018: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29708072/a-review-on-clinical-pharmacokinetics-pharmacodynamics-and-pharmacogenomics-of-natalizumab-a-humanized-anti-%C3%AE-4-integrin-monoclonal-antibody
#3
Li Hao, Shi Fang-Hong, Huang Shi-Ying, Zhang Shun-Guo, Chen Min-Ling
Natalizumab (Tysabri®, Biogen-Idec Inc., NAT), a humanized anti-α4 integrin monoclonal antibody, binds in both α4β1 (Very Late Antigen 4, VLA-4) and α4β7 (lymphocytes Peyer's patch adhesion molecule 1, LPAM-1) integrins, is approved for the treatment of Multiple sclerosis (MS) and Crohn's disease (CD). NAT has been well tolerated in pivotal trials. Progressive multifocal leukoencephalopathy (PML) is an uncommon but serious complications resulting from NAT treatment. It is not confirmed that higher NAT concentration increases the risk of PML...
April 27, 2018: Current Drug Metabolism
https://www.readbyqxmd.com/read/29705929/pharmacomicrobiomics-a-novel-route-towards-personalized-medicine
#4
REVIEW
Marwah Doestzada, Arnau Vich Vila, Alexandra Zhernakova, Debby P Y Koonen, Rinse K Weersma, Daan J Touw, Folkert Kuipers, Cisca Wijmenga, Jingyuan Fu
Inter-individual heterogeneity in drug response is a serious problem that affects the patient's wellbeing and poses enormous clinical and financial burdens on a societal level. Pharmacogenomics has been at the forefront of research into the impact of individual genetic background on drug response variability or drug toxicity, and recently the gut microbiome, which has also been called the second genome, has been recognized as an important player in this respect. Moreover, the microbiome is a very attractive target for improving drug efficacy and safety due to the opportunities to manipulate its composition...
April 28, 2018: Protein & Cell
https://www.readbyqxmd.com/read/29703433/points-to-consider-documents-scientific-information-on-the-evaluation-of-genetic-polymorphisms-during-non-clinical-studies-and-phase-i-clinical-trials-in-the-japanese-population
#5
REVIEW
Masahiro Hiratsuka, Noriyasu Hirasawa, Yoshiteru Oshima, Susumu Kodama, Toshio Miyata, Takashi Dan, Hiroyuki Takatoku, Hideaki Kuribayashi, Ryosuke Nakamura, Yoshiro Saito
Pharmacotherapy shows striking individual differences in pharmacokinetics and pharmacodynamics, involving drug efficacy and adverse reactions. Recent genetic research has revealed that genetic polymorphisms are important intrinsic factors for these inter-individual differences. This pharmacogenomic information could help develop safer and more effective precision pharmacotherapies and thus, regulatory guidance/guidelines were developed in this area, especially in the EU and US. The Project for the Promotion of Progressive Medicine, Medical Devices, and Regenerative Medicine by the Ministry of Health, Labour and Welfare, performed by Tohoku University, reported scientific information on the evaluation of genetic polymorphisms, mainly on drug metabolizing enzymes and transporters, during non-clinical studies and phase I clinical trials in Japanese subjects/patients...
March 15, 2018: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29691129/corrigendum-to-pharmacogenomics-of-drug-metabolizing-enzymes-and-transporters-relevance-to-precision-medicine-genomics-proteomics-bioinformatics-14-5-2016-298-313
#6
Shabbir Ahmed, Zhan Zhou, Jie Zhou, Shu-Qing Chen
No abstract text is available yet for this article.
April 21, 2018: Genomics, Proteomics & Bioinformatics
https://www.readbyqxmd.com/read/29678087/towards-pharmacogenomics-driven-medication-risk-assessment-in-people-with-polypharmacy
#7
Jiazhen Liu, Joseph Finkelstein
The main objective of this project was to introduce approaches for comprehensive medication risk assessment in people with polypharmacy that simultaneously account for multiple drug and gene effects. To achieve this goal, we developed an integrated knowledge repository of actionable pharmacogenes and a scoring algorithm that was pilot-tested using a data set containing pharmacogenomic information of people with polypharmacy. Metabolic phenotyping using resulting database demonstrated recall of 83.6% and precision of 87...
2018: Studies in Health Technology and Informatics
https://www.readbyqxmd.com/read/29663413/predicting-pharmacokinetics-pharmacodynamics-in-the-individual-patient-separating-reality-from-hype
#8
REVIEW
Leslie Z Benet
Individualization of patient drug dosing to maximize efficacy and minimize toxicity is the goal of clinical pharmacology. Here we review the history of drug dosing individualization from early predictions for renally eliminated drugs based on kidney function through the introduction of clearance concepts for metabolic processes, the differentiation of volume of distribution between pharmacokinetics and chemistry, the role of transporters, the unique pharmacokinetic aspects of oral dosing, and the relevance of protein binding to the emergence of pharmacogenomics...
April 17, 2018: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29652911/pharmacogenetic-landscape-of-metabolic-syndrome-components-drug-response-in-tunisia-and-comparison-with-worldwide-populations
#9
Haifa Jmel, Lilia Romdhane, Yosra Ben Halima, Meriem Hechmi, Chokri Naouali, Hamza Dallali, Yosr Hamdi, Jingxuan Shan, Abdelmajid Abid, Henda Jamoussi, Sameh Trabelsi, Lotfi Chouchane, Donata Luiselli, Sonia Abdelhak, Rym Kefi
Genetic variation is an important determinant affecting either drug response or susceptibility to adverse drug reactions. Several studies have highlighted the importance of ethnicity in influencing drug response variability that should be considered during drug development. Our objective is to characterize the genetic variability of some pharmacogenes involved in the response to drugs used for the treatment of Metabolic Syndrome (MetS) in Tunisia and to compare our results to the worldwide populations. A set of 135 Tunisians was genotyped using the Affymetrix Chip 6...
2018: PloS One
https://www.readbyqxmd.com/read/29651444/an-updated-review-of-the-molecular-mechanisms-in-drug-hypersensitivity
#10
REVIEW
Chun-Bing Chen, Riichiro Abe, Ren-You Pan, Chuang-Wei Wang, Shuen-Iu Hung, Yi-Giien Tsai, Wen-Hung Chung
Drug hypersensitivity may manifest ranging from milder skin reactions (e.g., maculopapular exanthema and urticaria) to severe systemic reactions, such as anaphylaxis, drug reactions with eosinophilia and systemic symptoms (DRESS)/drug-induced hypersensitivity syndrome (DIHS), or Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). Current pharmacogenomic studies have made important strides in the prevention of some drug hypersensitivity through the identification of relevant genetic variants, particularly for genes encoding drug-metabolizing enzymes and human leukocyte antigens (HLAs)...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/29520079/a-6-week-laboratory-research-rotation-in-pharmacogenomics-a-model-for-preparing-pharmacy-students-to-practice-precision-medicine
#11
Prema S Rao, Ryan Endicott, Randy Mullins, U Subrahmanyeswara Rao
Comparison of human genome sequences from different individuals has unraveled that genes involved in the drug efficacy and metabolism are polymorphic, harboring mutations, splicing variations and other alterations. These data provide a reasonable explanation for the inter-individual variations observed in drug therapy. Thus, a detailed molecular analysis and an in-depth knowledge of these genes is a prerequisite to practice pharmacogenomics-based medicine. We have introduced a 6-week laboratory research rotation to train students in the expression analysis of different pharmacogenes combined with bioinformatics tools...
March 8, 2018: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29496712/pharmacogenomics-in-critical-care
#12
Dennis Cheek, Lynnette Howington
Since the successful completion of the Human Genome Project in 2003, extensive genomic research has continued to alter pathophysiology at the molecular level. This research includes investigation of the specific receptors and metabolizing enzymes in drug pharmacodynamics and pharmacokinetics, specifically the cytochrome P450 system located primarily in the liver. In this article, pharmacogenomics and the role of the cytochrome P450 system in metabolism of various drugs are discussed. Specifically, drugs that are used in the critical care setting and are of clinical significance to the bedside critical care nurse are examined...
2018: AACN Advanced Critical Care
https://www.readbyqxmd.com/read/29462177/improving-stability-of-prediction-models-based-on-correlated-omics-data-by-using-network-approaches
#13
Renaud Tissier, Jeanine Houwing-Duistermaat, Mar Rodríguez-Girondo
Building prediction models based on complex omics datasets such as transcriptomics, proteomics, metabolomics remains a challenge in bioinformatics and biostatistics. Regularized regression techniques are typically used to deal with the high dimensionality of these datasets. However, due to the presence of correlation in the datasets, it is difficult to select the best model and application of these methods yields unstable results. We propose a novel strategy for model selection where the obtained models also perform well in terms of overall predictability...
2018: PloS One
https://www.readbyqxmd.com/read/29454235/donor-and-recipient-p450-gene-polymorphisms-influence-individual-pharmacological-effects-of-tacrolimus-in-chinese-liver-transplantation-patients
#14
Jianyu Liu, Yabo Ouyang, Dexi Chen, Bo Yao, Dongdong Lin, Zhiqiang Li, Yunjin Zang, Huan Liu, Xiaoyue Fu
The immunosuppressant drug tacrolimus (Tac) used for the prevention of immunological rejection is a metabolic substrate of cytochrome P450 enzymes. This study was designed to evaluate the short-term and long-term potential influence of single-nucleotide polymorphisms (SNPs) in CYP450 genes of liver transplant (LT) recipients as well as the donors on individual pharmacological effects of Tac and to guide individualized-medication from the perspective of pharmacogenomics. Twenty-one SNPs of the CYP450 gene were genotyped for both recipients and donors in 373 LT patients receiving Tac-based immunosuppressants...
April 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29450233/pharmacogenomics-guided-policy-in-opioid-use-disorder-oud-management-an-ethnically-diverse-case-based-approach
#15
Earl B Ettienne, Edwin Chapman, Mary Maneno, Adaku Ofoegbu, Bradford Wilson, Beverlyn Settles-Reaves, Melissa Clarke, Georgia Dunston, Kevin Rosenblatt
Introduction: Opioid use disorder (OUD) is characterized by a problematic pattern of opioid use leading to clinically-significant impairment or distress. Opioid agonist treatment is an integral component of OUD management, and buprenorphine is often utilized in OUD management due to strong clinical evidence for efficacy. However, interindividual genetic differences in buprenorphine metabolism may result in variable treatment response, leaving some patients undertreated and at increased risk for relapse...
December 2017: Addictive Behaviors Reports
https://www.readbyqxmd.com/read/29433307/role-of-hepatic-organic-anion-transporter-2-in-the-pharmacokinetics-of-r-and-s-warfarin-in-vitro-studies-and-mechanistic-evaluation
#16
Yi-An Bi, Jian Lin, Sumathy Mathialagan, Laurie Tylaska, Ernesto Callegari, A David Rodrigues, Manthena V S Varma
Interindividual variability in warfarin dose requirement demands personalized medicine approaches to balance its therapeutic benefits (anticoagulation) and bleeding risk. Cytochrome P450 2C9 ( CYP2C9) genotype-guided warfarin dosing is recommended in the clinic, given the more potent S-warfarin is primarily metabolized by CYP2C9. However, only about 20-30% of interpatient variability in S-warfarin clearance is associated with CYP2C9 genotype. We evaluated the role of hepatic uptake in the clearance of R- and S-warfarin...
March 5, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29413077/depression-and-pharmacogenetics
#17
David Nana Ampong
Depression is the most common and leading devastating psychiatric illness that affects a majority of the world population. The treatment of depression has been a challenge for a majority of patients and healthcare practitioners. The advent of pharmacogenomics (PGx) empowered the Food and Drug Administration to approve some antidepressant biomarkers for PGx model of treatment. The PGx testing identifies whether an individual is a poor metabolizer, ultra/rapid metabolizer, intermediate metabolizer, or essential metabolizer of an antidepressants before prescription...
February 2018: Archives of Psychiatric Nursing
https://www.readbyqxmd.com/read/29385765/pharmacogenomic-impact-of-cyp2c19-variation-on-clopidogrel-therapy-in-precision-cardiovascular-medicine
#18
REVIEW
Sherry-Ann Brown, Naveen Pereira
Variability in response to antiplatelet therapy can be explained in part by pharmacogenomics, particularly of the CYP450 enzyme encoded by CYP2C19 . Loss-of-function and gain-of-function variants help explain these interindividual differences. Individuals may carry multiple variants, with linkage disequilibrium noted among some alleles. In the current pharmacogenomics era, genomic variation in CYP2C19 has led to the definition of pharmacokinetic phenotypes for response to antiplatelet therapy, in particular, clopidogrel...
January 30, 2018: Journal of Personalized Medicine
https://www.readbyqxmd.com/read/29325731/pharmacogenomic-testing-in-child-and-adolescent-psychiatry-an-evidence-based-review
#19
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 2A receptor genes (e...
February 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
#20
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
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