Read by QxMD icon Read

Pharmacogenomics drugs metabolism

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
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
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
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...
February 14, 2018: International Immunopharmacology
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
Yi-An Bi, Jian Lin, Sumathy Mathialagan, Laurie Tylaska, Ernesto Callegari, A David Rodrigues, Manthena V S Varma
Inter-individual 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 inter-patient 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...
February 12, 2018: Molecular Pharmaceutics
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
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
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
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
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
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
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
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...
February 2018: Pharmacotherapy
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
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
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...
December 2017: Pharmacogenomics
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
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
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
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"