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Pharmacogenomics drugs metabolism

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https://www.readbyqxmd.com/read/29099060/clinical-pharmacogenetics-of-cytochrome-p450-associated-drugs-in-children
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
https://www.readbyqxmd.com/read/28766962/clarifying-busulfan-metabolism-and-drug-interactions-to-support-new-therapeutic-drug-monitoring-strategies-a-comprehensive-review
#10
REVIEW
Alan L Myers, Jitesh D Kawedia, Richard E Champlin, Mark A Kramer, Yago Nieto, Romi Ghose, Borje S Andersson
Busulfan (Bu) is an alkylating agent with a limited therapeutic margin and exhibits inter-patient variability in pharmacokinetics (PK). Despite decades of use, mechanisms of Bu PK-based drug-drug interactions (DDIs), as well as the negative downstream effects of these DDIs, have not been fully characterized. Areas covered: This article provides an overview of Bu PK, with a primary focus on how known and potentially unknown drug metabolism pathways influence Bu-associated DDIs. In addition, pharmacogenomics of Bu chemotherapy and Bu-related DDIs observed in the stem cell transplant clinic (SCT) are summarized...
September 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28748996/clinical-applications-of-pharmacogenomics
#11
REVIEW
Luis Quiñones, Ángela Roco, Juan P Cayún, Paula Escalante, Carla Miranda, Nelson Varela, Francisca Meneses, Bastián Gallegos, Fausto Zaruma-Torres, Ismael Lares-Asseff
Pharmacogenomics is an emergent field aimed at tailoring pharmacological therapy. Genetic polymorphisms can modify the expression and function of enzymes and proteins involved in drug metabolism, affecting absorption, distribution, biotransformation and excretion as well as the drug-target interaction. Therefore, the presence of allelic variants will classify people as poor, extensive or rapid/ultra rapid metabolizers, modifying drug efficacy and safety. In this work, the state of art in relation to this discipline is presented and the genetic variants of enzymes that are involved in drug pharmacokinetics or pharmacodynamics are described...
April 2017: Revista Médica de Chile
https://www.readbyqxmd.com/read/28748348/impact-of-genetic-polymorphisms-on-phenytoin-pharmacokinetics-and-clinical-outcomes-in-the-middle-east-and-north-africa-region
#12
REVIEW
Renée Dagenais, Kyle John Wilby, Hazem Elewa, Mary H H Ensom
BACKGROUND: Genetic polymorphisms are known to influence outcomes with phenytoin yet effects in the Middle East and North Africa region are poorly understood. OBJECTIVES: The objective of this systematic review was to evaluate the impact of genetic polymorphisms on phenytoin pharmacokinetics and clinical outcomes in populations originating from the Middle East and North Africa region, and to characterize genotypic and allelic frequencies within the region for genetic polymorphisms assessed...
July 26, 2017: Drugs in R&D
https://www.readbyqxmd.com/read/28723497/pharmacogenomic-markers-of-targeted-therapy-toxicity-in-patients-with-metastatic-renal-cell-carcinoma
#13
Guillermo de Velasco, Kathryn P Gray, Lana Hamieh, Yuksel Urun, Hallie A Carol, Andre P Fay, Sabina Signoretti, David J Kwiatkowski, David F McDermott, Matthew Freedman, Mark M Pomerantz, Toni K Choueiri
BACKGROUND: Targeted therapy (TT) in metastatic renal cell carcinoma (mRCC) may be associated with a high rate of toxicity that undermines treatment efficacy and patient quality of life. Polymorphisms in genes involved in the pharmacokinetic pathways of TTs may predict toxicity. OBJECTIVE: To investigate whether selected single-nucleotide polymorphisms (SNPs) in three core genes involved in the metabolism and transport of sunitinib and the mTOR inhibitors everolimus and temsirolimus are associated with adverse events (AEs)...
December 15, 2016: European Urology Focus
https://www.readbyqxmd.com/read/28719598/the-predictive-value-of-abcb1-abcg2-cyp3a4-5-and-cyp2d6-polymorphisms-for-risperidone-and-aripiprazole-plasma-concentrations-and-the-occurrence-of-adverse-drug-reactions
#14
C Rafaniello, M Sessa, F F Bernardi, M Pozzi, S Cheli, D Cattaneo, S Baldelli, M Molteni, R Bernardini, F Rossi, E Clementi, C Bravaccio, S Radice, A Capuano
We investigated in ninety Caucasian pediatric patients the impact of the main polymorphisms occurring in CYP3A, CYP2D6, ABCB1 and ABCG2 genes on second-generation antipsychotics plasma concentrations, and their association with the occurrence of adverse drug reactions. Patients with the CA/AA ABCG2 genotype had a statistically significant lower risperidone plasma concentration/dose ratio (Ct/ds) (P-value: 0.007) and an higher estimated marginal probability of developing metabolism and nutrition disorders as compared to the ABCG2 c...
July 18, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28698977/pharmacogenetics-and-pharmacogenomics-of-targeted-therapeutics-in-chronic-myeloid-leukemia
#15
REVIEW
Aritro Nath, Jacqueline Wang, R Stephanie Huang
The advent of targeted therapeutics has greatly improved outcomes of chronic myeloid leukemia (CML) patients. Despite increased efficacy and better clinical responses over cytotoxic chemotherapies, many patients receiving targeted drugs exhibit a poor initial response, develop drug resistance, or undergo relapse after initial success. This inter-individual variation in response has heightened the interest in studying pharmacogenetics and pharmacogenomics (PGx) of cancer drugs. In this review, we discuss the influence of various germline and somatic factors on targeted drug response in CML...
July 11, 2017: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/28689706/the-innovative-canadian-pharmacogenomic-screening-initiative-in-community-pharmacy-icanpic-study
#16
John Papastergiou, Peter Tolios, Wilson Li, Jane Li
OBJECTIVES: The safety and efficacy of medications can vary significantly between patients as a result of genetic variability. As genomic screening technologies become more widely available, pharmacists are ideally suited to use such tools to optimize medication therapy management. The objective of this study was to evaluate the feasibility of implementing personalized medication services into community pharmacy practice and to assess the number of drug therapy problems identified as a result of pharmacogenomic screening...
July 6, 2017: Journal of the American Pharmacists Association: JAPhA
https://www.readbyqxmd.com/read/28669097/medical-education-in-pharmacogenomics-results-from-a-survey-on-pharmacogenetic-knowledge-in-healthcare-professionals-within-the-european-pharmacogenomics-clinical-implementation-project-ubiquitous-pharmacogenomics-u-pgx
#17
Katja Susanne Just, Michael Steffens, Jesse Joachim Swen, George P Patrinos, Henk-Jan Guchelaar, Julia Carolin Stingl
PURPOSE: Due to the diversity within Europe, the implementation of pharmacogenomic testing in clinical practice faces specific challenges. In the context of the European pharmacogenomics implementation project "Ubiquitous Pharmacogenomics" (U-PGx; funded by the European Commission), we studied the current educational background. METHODS: We developed a questionnaire including 29 questions. It was spread out to healthcare professionals working at the future implementation sites (in Austria, Greece, Italy, Netherlands, Slovenia, Spain and Great Britain) of the U-PGx project in preparation of an educational programme...
July 2, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28655393/the-role-of-single-nucleotide-polymorphisms-of-cyp3a-and-abcb1-on-tacrolimus-predose-concentration-in-kidney-transplant-recipients
#18
Gregor Mlinšek, Vita Dolžan, Katja Goričar, Jadranka Buturović-Ponikvar, Miha Arnol
BACKGROUND: Tacrolimus has a narrow therapeutic drug window but high inter- and intrapatient variability. Our aim is to construct a model able to predict optimal maintenance tacrolimus predose concentration (C0) in kidney transplant patients. Here we present our study design and genotype and variant allele frequencies for the selected single nucleotide polymorphisms of genes involved in tacrolimus metabolism in our national cohort of kidney transplant recipients. METHODS: In the observational part of the study, we intend to determine allelic variants of CYP3A4, CYP3A5, and ABCB1 gene in a national cohort of 700 kidney transplants recipients...
June 28, 2017: Clinical Nephrology
https://www.readbyqxmd.com/read/28640195/pharmacogenomic-variants-may-influence-the-urinary-excretion-of-novel-kidney-injury-biomarkers-in-patients-receiving-cisplatin
#19
Cara Chang, Yichun Hu, Susan L Hogan, Nickie Mercke, Madeleine Gomez, Cindy O'Bryant, Daniel W Bowles, Blessy George, Xia Wen, Lauren M Aleksunes, Melanie S Joy
Nephrotoxicity is a dose limiting side effect associated with the use of cisplatin in the treatment of solid tumors. The degree of nephrotoxicity is dictated by the selective accumulation of cisplatin in renal tubule cells due to: (1) uptake by organic cation transporter 2 (OCT2) and copper transporter 1 (CTR1); (2) metabolism by glutathione S-transferases (GSTs) and γ-glutamyltransferase 1 (GGT1); and (3) efflux by multidrug resistance-associated protein 2 (MRP2) and multidrug and toxin extrusion protein 1 (MATE1)...
June 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28607505/predictive-genetic-markers-in-neoadjuvant-chemoradiotherapy-for-locally-advanced-esophageal-cancer-a-long-way-to-go-review-of-the-literature
#20
REVIEW
M Gusella, E Pezzolo, Y Modena, C Barile, D Menon, G Crepaldi, F La Russa, A P Fraccon, F Pasini
The role of genetic molecular markers in neoadjuvant treatment for locally advanced esophageal cancer has been reviewed, focusing strictly on concurrent chemoradiation protocols followed by surgery. Eleven studies evaluated the role of mRNA expression profile; the end point was overall survival (OS) in two studies and different definitions of histological response in nine. Genes reported as significant were involved in cell cycle control (30), apoptosis (7), structural molecules (9), cell metabolism (6) and DNA repair (1)...
June 13, 2017: Pharmacogenomics Journal
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