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Pharmacogenomics drugs metabolism

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https://www.readbyqxmd.com/read/28210221/pharmacogenomic-characterization-and-isobologram-analysis-of-the-combination-of-ascorbic-acid-and-curcumin-two-main-metabolites-of-curcuma-longa-in-cancer-cells
#1
Edna Ooko, Onat Kadioglu, Henry J Greten, Thomas Efferth
Curcuma longa has long been used in China and India as anti-inflammatory agent to treat a wide variety of conditions and also as a spice for varied curry preparations. The chemoprofile of the Curcuma species exhibits the presence of varied phytochemicals with curcumin being present in all three species but AA only being shown in C. longa. This study explored the effect of a curcumin/AA combination on human cancer cell lines. The curcumin/AA combination was assessed by isobologram analysis using the Loewe additivity drug interaction model...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28176639/personalized-medicine-in-the-paediatric-population-the-balance-between-pharmacogenetics-progress-and-bioethics
#2
Stefania Schiavone, Margherita Neri, Cristoforo Pomara, Irene Riezzo, Luigia Trabace, Emanuela Turillazzi
Personalized medicine (PM) is becoming increasingly important in contemporary clinical and research scenarios. In the context of PM, pharmacogenomics and pharmacogenetics are aimed at the genetic personalization of drug response. Extrinsic and intrinsic factors may explain inter-individual variability in drug response. Among such factors, age seems to specifically intervene to modulate drug response since normal developmental changes may influence the exposure-response relation. Consequently, the potential benefit of pharmacogenomics (PGx) in the paediatric population is considerable...
February 7, 2017: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/28159880/en-route-to-precision-medicine-through-the-integration-of-biological-sex-into-pharmacogenomics
#3
REVIEW
Lea Gaignebet, Georgios Kararigas
Frequently, pharmacomechanisms are not fully elucidated. Therefore, drug use is linked to an elevated interindividual diversity of effects, whether therapeutic or adverse, and the role of biological sex has as yet unrecognized and underestimated consequences. A pharmacogenomic approach could contribute towards the development of an adapted therapy for each male and female patient, considering also other fundamental features, such as age and ethnicity. This would represent a crucial step towards precision medicine and could be translated into clinical routine...
February 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28046094/analysis-of-genetic-variation-in-cyp450-genes-for-clinical-implementation
#4
Liuh Ling Goh, Chia Wei Lim, Wey Cheng Sim, Li Xian Toh, Khai Pang Leong
BACKGROUND: Genetic determinants of drug response remain stable throughout life and offer great promise to patient-tailored drug therapy. The adoption of pharmacogenetic (PGx) testing in patient care requires accurate, cost effective and rapid genotyping with clear guidance on the use of the results. Hence, we evaluated a 32 SNPs panel for implementing PGx testing in clinical laboratories. METHODS: We designed a 32-SNP panel for PGx testing in clinical laboratories...
2017: PloS One
https://www.readbyqxmd.com/read/28045128/epigenomics-alternations-and-dynamic-transcriptional-changes-in-responses-to-5-fluorouracil-stimulation-reveal-mechanisms-of-acquired-drug-resistance-of-colorectal-cancer-cells
#5
Y Shen, M Tong, Q Liang, Y Guo, H Q Sun, W Zheng, L Ao, Z Guo, F She
A drug-induced resistant cancer cell is different from its parent cell in transcriptional response to drug treatment. The distinct transcriptional response pattern of a drug-induced resistant cancer cell to drug treatment might be introduced by acquired DNA methylation aberration in the cell exposing to sustained drug stimulation. In this study, we performed both transcriptional and DNA methylation profiles of the HCT-8 wild-type cells (HCT-8/WT) for human colorectal cancer (CRC) and the 5-fluorouracil (5-FU)-induced resistant cells (HCT-8/5-FU) after treatment with 5-FU for 0, 24 and 48 h...
January 3, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28018217/pharmacogenomic-study-reveals-new-variants-of-drug-metabolizing-enzyme-and-transporter-genes-associated-with-steady-state-plasma-concentrations-of-risperidone-and-9-hydroxyrisperidone-in-thai-autism-spectrum-disorder-patients
#6
Sadeep Medhasi, Darawan Pinthong, Ekawat Pasomsub, Natchaya Vanwong, Nattawat Ngamsamut, Apichaya Puangpetch, Monpat Chamnanphon, Yaowaluck Hongkaew, Jirawat Pratoomwun, Penkhae Limsila, Chonlaphat Sukasem
The present study sought to investigate the genetic variants in drug metabolizing enzyme and transporter (DMET) genes associated with steady-state plasma concentrations of risperidone among Thai autism spectrum disorder (ASD) patients. ASD patients taking risperidone for at least 1 month were enrolled for this pharmacogenomic study. Genotyping profile was obtained using Affymetrix DMET Plus array interrogating 1931 variants in 231 genes. Steady-state plasma risperidone and 9-hydroxyrisperidone were measured using liquid chromatography/tandem mass spectrometry assay...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27957864/drug-metabolism-and-liver-disease-a-drug-gene-environment-interaction
#7
Nathalie K Zgheib, Robert A Branch
Despite the central role of the liver in drug metabolism, surprisingly there is lack of certainty in anticipating the extent of modification of the clearance of a given drug in a given patient. The intent of this review is to provide a conceptual framework in considering the impact of liver disease on drug disposition and reciprocally the impact of drug disposition on liver disease. It is proposed that improved understanding of the situation is gained by considering the issue as a special example of a drug-gene-environment interaction...
January 23, 2017: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/27942231/cyp2d6-polymorphisms-and-their-influence-on-risperidone-treatment
#8
REVIEW
Apichaya Puangpetch, Natchaya Vanwong, Nopphadol Nuntamool, Yaowaluck Hongkaew, Monpat Chamnanphon, Chonlaphat Sukasem
Cytochrome P450 enzyme especially CYP2D6 plays a major role in biotransformation. The interindividual variations of treatment response and toxicity are influenced by the polymorphisms of this enzyme. This review emphasizes the effect of CYP2D6 polymorphisms in risperidone treatment in terms of basic knowledge, pharmacogenetics, effectiveness, adverse events, and clinical practice. Although the previous studies showed different results, the effective responses in risperidone treatment depend on the CYP2D6 polymorphisms...
2016: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/27935783/the-role-of-pharmacogenomics-in-anesthesia-pharmacology
#9
Brett Morgan, Edwin N Aroke, Jennifer Dungan
The field of pharmacogenomics seeks to identify the impact of genetic variants on drug dosing, response, metabolism, and safety outcomes. The narrow therapeutic indices for anesthesia drugs, variability of patient responses to anesthesia, and the risks associated with surgery make anesthetics and the perioperative period prime targets for pharmacogenetic research. Anesthesia providers strive to optimize anesthesia delivery and patient outcomes and to specifically reduce anesthesia-related risks and negative outcomes...
January 2017: Annual Review of Nursing Research
https://www.readbyqxmd.com/read/27918238/genome-wide-mirnas-expression-profiles-of-schistosoma-japonicum-schistosomula-in-response-to-artesunate
#10
Qing-Ming Kong, Xiao Zhu, Qun-Bo Tong, Bin Zheng, Na-Yu Shi, Di Lou, Jian-Zu Ding, Jian-Ping Jia, Xiao-Heng Chen, Rui Chen, Shao-Hong Lu
AIM: miRNAs play a significant role in pharmacogenomics and are likely to be important in the molecular mechanism of atesunate (ART) effects on Schistosoma japonicum. METHODS: We sequenced the RNAs using an Illumina (Solexa) DNA sequencer and compared the relative expression levels of the miRNAs in 10-day-old schistosomula from ART and the parallel control group. RESULTS: We characterized 95 known miRNAs from S. japonicum schistosomula individuals, including 38 novel miRNA families...
December 2016: Pharmacogenomics
https://www.readbyqxmd.com/read/27915083/pharmacodynamic-and-cytogenetic-evaluation-in-cyp2c19-2-and-cyp2c19-3-allelomorphism-in-south-indian-population-with-clopidogrel-therapy
#11
Javeed Ahmad Tantray, K Pratap Reddy, Kaiser Jamil, Y Shiva Kumar
BACKGROUND: Genetic factors play a significant role in pathogenesis of most diseases of heart. The present study was undertaken to correlate coronary artery disease with demographical, biochemical alterations, SNPs, gene expression and chromosomal abnormalities and for further enlightening the investigation in this field. METHODS: 150 patients taking clopidogrel drug were selected and single nucleotide polymorphism was done by PCR-RFLP techniques. With the same patients cytogenetic analysis was carried out on leukocyte cultures by karyotyping...
February 15, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/27897267/increasing-bmi-is-associated-with-reduced-expression-of-p-glycoprotein-abcb1-gene-in-the-human-brain-with-a-stronger-association-in-african-americans-than-caucasians
#12
J Vendelbo, R H Olesen, J K Lauridsen, J Rungby, J E Kleinman, T M Hyde, A Larsen
The efflux pump, p-glycoprotein, controls bioavailability and excretion of pharmaceutical compounds. In the blood-brain barrier, p-glycoprotein regulates the delivery of pharmaceutical substances to the brain, influencing efficacy and side effects for some drugs notably antipsychotics. Common side effects to antipsychotics include obesity and metabolic disease. Polymorphisms in the ABCB1 gene coding for p-glycoprotein are associated with more severe side effects to neuro-pharmaceuticals as well as weight gain, indicating a potential link between p-glycoprotein function and metabolic regulation...
November 29, 2016: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/27871989/quality-by-design-qbd-approach-of-pharmacogenomics-in-drug-designing-and-formulation-development-for-optimization-of-drug-delivery-systems
#13
REVIEW
Sumeet Gupta, Vikas Jhawat
Conventional approaches of drug discovery are very complex, costly and time consuming. But after the completion of human genome project, applications of pharmacogenomics in this area completely revolutionize the drug discovery and development process to produce a quality by design (QbD) approach based products. The applications of two areas of pharmacogenomics i.e. structural and functional pharmacogenomics excel the drug discovery process by employing genomic data in drug target identification and evaluation, lead optimization via high throughput screening, evaluation of drug metabolizing enzymes, drug transporters and drug receptors using computer aided technique and bioinformatics library data base...
November 19, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/27861439/trends-in-tramadol-pharmacology-metabolism-and-misuse
#14
Karen Miotto, Arthur K Cho, Mohamed A Khalil, Kirsten Blanco, Jun D Sasaki, Richard Rawson
Tramadol is a unique analgesic medication, available in variety of formulations, with both monoaminergic reuptake inhibitory and opioid receptor agonist activity increasingly prescribed worldwide as an alternative for high-affinity opioid medication in the treatment of acute and chronic pain. It is a prodrug that is metabolized by cytochrome P450 (CYP) enzymes CYP2D6 and CYP3A4 to its more potent opioid analgesic metabolites, particularly the O-demethylation product M1. The opioid analgesic potency of a given dose of tramadol is influenced by an individual's CYP genetics, with poor metabolizers experiencing little conversion to the active M1 opioid metabolite and individuals with a high metabolic profile, or ultra-metabolizers, experiencing the greatest opioid analgesic effects...
January 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/27854302/severe-cutaneous-adverse-reactions-the-pharmacogenomics-from-research-to-clinical-implementation
#15
REVIEW
Shih-Chi Su, Shuen-Iu Hung, Wen-Lang Fan, Ro-Lan Dao, Wen-Hung Chung
Severe cutaneous adverse reactions (SCARs), previously thought to be idiosyncratic or unpredictable, are a deadly form of adverse drug reactions with skin manifestations. Current pharmacogenomic studies of SCARs have made important strides, as the prevention of SCARs, to some extent, appears attainable with the identification of genetic variants for genes encoding drug-metabolizing enzymes and human leukocyte antigens (HLAs). Despite the improvement of incidence, a treatment guideline for this devastating condition is still unavailable, highlighting the inadequacy of contemporary accepted therapeutic interventions...
November 15, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27849442/to-genotype-or-phenotype-for-personalized-medicine-cyp450-drug-metabolizing-enzyme-genotype-phenotype-concordance-and-discordance-in-the-ecuadorian-population
#16
Fernando De Andrés, Santiago Terán, Francisco Hernández, Enrique Terán, Adrián LLerena
Genetic variations within the cytochrome P450 (CYP450) superfamily of drug metabolizing enzymes confer substantial person-to-person and between-population differences in pharmacokinetics, and by extension, highly variable clinical effects of medicines. In this context, "personalized medicine," "precision medicine," and "stratified medicine" are related concepts attributed to what is essentially targeted therapeutics and companion diagnostics, aimed at improving safety and effectiveness of health interventions...
December 2016: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/27790935/pharmacogenetics-and-ethnicity-relevance-for-clinical-implementation-clinical-trials-pharmacovigilance-and-drug-regulation-in-latin-america
#17
Martha Sosa-Macías, Enrique Teran, William Waters, Martha M Fors, Catalina Altamirano, Helgi Jung-Cook, Carlos Galaviz-Hernández, Marisol López-López, Diadelis Remírez, Graciela E Moya, Francisco Hernández, Humberto Fariñas, Ronald Ramírez, Carolina Céspedes-Garro, Eduardo Tarazona-Santos, Adrián LLerena
Congress of Pharmacogenetics and Personalized Medicine. Ethnicity, clinical implementation and regulatory environment (MESTIFAR 2016 Quito). Quito, Ecuador, 19-21 May 2016. The Ibero-American Network of Pharmacogenetics and Pharmacogenomics (RIBEF) was created in 2006 with the main aim of promoting personalized medicine and collaborative pharmacogenetics research in Spanish- and Portuguese-speaking countries in America and the Iberian Peninsula. The final goal of this initiative was the inclusion of Latin American populations that may benefit from the implementation of personalized medicine in drug therapy...
October 28, 2016: Pharmacogenomics
https://www.readbyqxmd.com/read/27771974/new-treatment-strategies-for-hiv-positive-cancer-patients-undergoing-antiblastic-chemotherapy
#18
REVIEW
Massimiliano Berretta, Raffaele Di Francia, Brigida Stanzione, Gaetano Facchini, Arben LLeshi, Paolo De Paoli, Michele Spina, Umberto Tirelli
The introduction of Highly Active Antiretroviral Therapy (HAART) into clinical practice has dramatically changed the outcome of HIV-infected patients by prolonging their survival. The increase in life expectancy has led to an increased risk of non-AIDS-related mortality and morbidity, including cardiovascular diseases, neurocognitive diseases, neuroendocrine dysfunctions and cancer. Areas covered: The GICAT (Italian Cooperation Group on AIDS and Tumors) has demonstrated that patients who receive a multidisciplinary approach with the combination of anticancer agents (AC) and HAART can achieve better responses and survival rates than patients who receive AC alone...
December 2016: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/27767376/pharmacogenomics-and-histone-deacetylase-inhibitors
#19
Andrew Kl Goey, Tristan M Sissung, Cody J Peer, William D Figg
The histone deacetylase inhibitor valproic acid (VPA) has been used for many decades in neurology and psychiatry. The more recent introduction of the histone deacetylase inhibitors (HDIs) belinostat, romidepsin and vorinostat for treatment of hematological malignancies indicates the increasing popularity of these agents. Belinostat, romidepsin and vorinostat are metabolized or transported by polymorphic enzymes or drug transporters. Thus, genotype-directed dosing could improve pharmacotherapy by reducing the risk of toxicities or preventing suboptimal treatment...
October 21, 2016: Pharmacogenomics
https://www.readbyqxmd.com/read/27761138/dissecting-the-effect-of-genetic-variation-on-the-hepatic-expression-of-drug-disposition-genes-across-the-collaborative-cross-mouse-strains
#20
Aharon Nachshon, Hanifa J Abu-Toamih Atamni, Yael Steuerman, Roa'a Sheikh-Hamed, Alexandra Dorman, Richard Mott, Juliane C Dohm, Hans Lehrach, Marc Sultan, Ron Shamir, Sascha Sauer, Heinz Himmelbauer, Fuad A Iraqi, Irit Gat-Viks
A central challenge in pharmaceutical research is to investigate genetic variation in response to drugs. The Collaborative Cross (CC) mouse reference population is a promising model for pharmacogenomic studies because of its large amount of genetic variation, genetic reproducibility, and dense recombination sites. While the CC lines are phenotypically diverse, their genetic diversity in drug disposition processes, such as detoxification reactions, is still largely uncharacterized. Here we systematically measured RNA-sequencing expression profiles from livers of 29 CC lines under baseline conditions...
2016: Frontiers in Genetics
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