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https://www.readbyqxmd.com/read/29134945/drug-drug-interaction-potential-of-the-hepatitis-b-and-hepatitis-d-virus-entry-inhibitor-myrcludex-b-assessed-in-vitro
#1
Antje Blank, Katrin Meier, Stephan Urban, Walter Emil Haefeli, Johanna Weiss
BACKGROUND: Myrcludex B is a first-in-class virus entry inhibitor for patients with chronic hepatitis B or B/D infections. In patients it will be co-administered with drugs needed for the disease or comorbidities. We aimed to define the risk of drug-drug interactions by characterizing the influence of myrcludex B on relevant drug transporting and metabolizing enzymes in vitro. METHODS: Inhibition of P-glycoprotein (P-gp, ABCB1), breast cancer resistance protein (BCRP/ABCG2), and the organic anion transporting polypeptides 1B1 and 1B3 (OATP1B1/SLCO1B1 and OATP1B3/SLCO1B3) was measured in cells over-expressing the respective transporter using fluorogenic substrates...
November 14, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/29095107/slco1b1-rs4149056-genetic-polymorphism-predicting-methotrexate-toxicity-in-chinese-patients-with-non-hodgkin-lymphoma
#2
Lin Yang, Hui Wu, Teun van Gelder, Maja Matic, Jun-Shan Ruan, Yong Han, Rui-Xiang Xie
AIM: To investigate the impact of polymorphisms in the FPGS, GGH and SLCO1B1 genes on high dose methotrexate (HD-MTX) related toxicity in Chinese patients with non-Hodgkin lymphoma (NHL). MATERIALS & METHODS: We analyzed FPGS (rs10106), GGH (rs719235, rs10464903, rs12681874), SLCO1B1 (rs4149056) genetic polymorphisms in 105 Chinese patients with NHL treated with HD-MTX. RESULTS: There was a statistically significant impact of the SLCO1B1 rs4149056 polymorphism on hepatotoxicity...
November 2, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/29090664/pharmacogenetics-of-metabolic-genes-of-anthracyclines-in-acute-myeloid-leukemia
#3
Juan Eduardo Megias-Vericat, David Martinez-Cuadron, Maria Jose Herrero, Salvador F Alino, Jose Luis Poveda, Miguel Angel Sanz, Pau Montesinos
BACKGROUND: Anthracyclines in combination with cytarabine have been the standard therapy for acute myeloid leukemia (AML) for decades with high efficacy. However, the majority of patients will show initial resistance or will relapse after initial complete remission. Genetic variability in genes involved in anthracyclines metabolic pathway could be one of the causes of the interindividual differences in clinical outcomes. METHODS: A systematic review of published studies in AML cohorts was carried out in order to analyze the influence of polymorphisms in genes of anthracycline metabolism on efficacy and toxicity...
November 1, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/29039339/effects-of-two-functionally-important-slco1b1-gene-polymorphisms-on-pharmacokinetics-of-atorvastatin
#4
Tausif Ahmed Rajput, Abdul Khaliq Naveed, Ziaur Rehman Farooqi, Shakir Khan
Organic anion transporter polypeptide 1B1 (OATP1B1) encoded by (SLCO1B1) gene, an uptake transporter involved in the transport of drugs and endogenous compounds and located in hepatocyte sinusoidal membrane. Objective of study was to investigate the effects of two functionally significant SNPs (388A>G and 521T>C) and their respective genotypes of SLCO1B1 gene encoding OATP1B1 on the pharmacokinetics of atorvastatin. A total of 100 subjects divided into 6 groups as per their genotype profile were recruited...
July 2017: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29023140/genetic-polymorphisms-of-cytochrome-p450-enzymes-and-transport-proteins-in-a-russian-population-and-three-ethnic-groups-of-dagestan
#5
Karin B Mirzaev, Dmitry A Sychev, Kristina A Ryzhikova, Olga D Konova, Suleiman N Mammaev, Daniyal M Gafurov, Grigorij N Shuev, Elena A Grishina, Zhannet A Sozaeva
AIM: The objective of this study was to investigate the prevalence of polymorphic markers of the CYP2C19, CYP2C9, CYP2D6, SLCO1B1, and ABCB1 genes among the three ethnic groups in Dagestan and compare it with the carrier frequency of these markers among the Russian population living in Moscow. METHODS: The study involved 186 healthy, unrelated, and chronic medication-free volunteers (53 males and 133 females) of the three ethnic groups in the Dagestan Republic: 46 Laks, 90 Avars, and 50 Dargins...
October 12, 2017: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/28994310/pharmacogenetic-considerations-for-hiv-treatment-in-different-ethnicities-an-update
#6
REVIEW
M Neary, A Owen
Variations in the human genome sequence sometimes play an important role in pharmacokinetics and/or pharmacodynamics. Previous studies have demonstrated a high degree of variation both between and within different ethnic populations. Areas covered: This review sought to summarize key SNPs in CYP2B6, CYP3A enzymes, CYP2C enzymes, UGT2 enzymes, ABCB1, ABCC2, SLCO1B1, NR1I2, and NR1I3 that have previously been associated with variability in antiretroviral pharmacokinetics. Additionally, the impact of ethnicity in these pharmacogenetics studies is discussed, and variation in findings between different ethnic groups is reviewed...
November 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28975866/slco1a2-slco1b1-and-slco2b1-polymorphisms-influences-chloroquine-and-primaquine-treatment-in-plasmodium-vivax-malaria
#7
Vinicius A Sortica, Juliana D Lindenau, Maristela G Cunha, Maria Deise O Ohnishi, Ana Maria R Ventura, Ândrea Kc Ribeiro-Dos-Santos, Sidney Eb Santos, Luciano Sp Guimarães, Mara H Hutz
AIM: The association of transporters gene polymorphisms with chloroquine/primaquine malaria treatment response was investigated in a Brazilian population. PATIENTS & METHODS: Totally, 164 Plasmodium vivax malaria infected patients were included. Generalized estimating equations were performed to determine gene influences on parasitemia and/or gametocytemia clearance over treatment time. RESULTS: Significant interaction between SLCO2B1 genotypes and treatment over time for parasitemia clearance rate on day 2 were observed (p FDR = 0...
October 4, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28940478/comprehensive-pharmacogenomic-study-reveals-an-important-role-of-ugt1a3-in-montelukast-pharmacokinetics
#8
Päivi Hirvensalo, Aleksi Tornio, Mikko Neuvonen, Tuija Tapaninen, Maria Paile-Hyvärinen, Vesa Kärjä, Ville T Männistö, Jussi Pihlajamäki, Janne T Backman, Mikko Niemi
To identify genetic basis of interindividual variability in montelukast exposure, we determined its pharmacokinetics and sequenced 379 pharmacokinetic genes in 191 healthy volunteers. An intronic single nucleotide variation (SNV), strongly linked with UGT1A3*2, associated with reduced area under the plasma concentration-time curve (AUC0-∞ ) of montelukast (by 18% per copy of the minor allele; P=1.83 × 10(-10) ). UGT1A3*2 associated with increased AUC0-∞ of montelukast acyl-glucuronide M1 and decreased AUC0-∞ of hydroxymetabolites M5R, M5S, and M6 (P<10(-9) )...
September 23, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28940218/genetic-and-clinical-factors-are-associated-with-statin-related-myotoxicity-of-moderate-severity-a-case-control-study
#9
Nur Salwani Bakar, Dermot Neely, Peter Avery, Colin Brown, Ann K Daly, Farhad Kamali
We evaluated the contribution of patient specific clinical and genetic factors to statin-related muscle toxicity (SRM) without significant creatine kinase elevation (125 cases related to simvastatin or atorvastatin and 481 controls). The association between 12 SNPs in nine candidate genes and clinical factors with SRM was evaluated. Of the 12 SNPs genotyped, only rs4149056 in SLCO1B1 was associated with SRM in univariate analysis (with any statin, OR=1.73, 95% CI= 1.14-2.62, P = 0.010) and this association was influenced by sex (P= 0...
September 22, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28921647/pharmacogenomics-implementation-at-the-national-institutes-of-health-clinical-center
#10
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/28900877/genetic-polymorphisms-of-slco1b1-cyp2e1-and-ugt1a1-and-susceptibility-to-anti-tuberculosis-drug-induced-hepatotoxicity-a-chinese-population-based-prospective-case-control-study
#11
Qin Sun, Hai-Peng Liu, Rui-Juan Zheng, Peng Wang, Zhi-Bin Liu, Wei Sha, He-Ping Xiao
BACKGROUND: Drug transporters and drug-metabolizing enzymes have been linked to drug-induced hepatotoxicity. Solute carrier organic anion transporter family member 1B1 (SLCO1B1), cytochrome P450 2E1 (CYP2E1), and UDP glucuronosyltransferase 1A1 (UGT1A1) were selected as candidate genes to explore their association with susceptibility to anti-tuberculosis drug-induced hepatotoxicity (ATDH). METHODS: Thirty-four tag single nucleotide polymorphisms (tagSNPs) in SLCO1B1, CYP2E1, and UGT1A1 with 10-kb expansion up- and down-stream were genotyped in 461 patients with ATDH and 466 patients without ATDH in a prospective 1:1 matched case-control study...
December 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/28887233/methotrexate-pharmacogenetics-in-uruguayan-adults-with-hematological-malignant-diseases
#12
Andrea Giletti, Marcelo Vital, Mariana Lorenzo, Patricia Cardozo, Gabriel Borelli, Raúl Gabus, Lem Martínez, Lilian Díaz, Rodrigo Assar, María Noel Rodriguez, Patricia Esperón
BACKGROUND: Individual variability is among the causes of toxicity and interruption of treatment in acute lymphoblastic leukemia (ALL) and severe non-Hodgkin lymphoma (NHL) patients under protocols including Methotrexate (MTX): 2,4-diamino-N10-methyl propyl-glutamic acid. METHODS: 41 Uruguayan patients were recruited. Gene polymorphisms involved in MTX pathway were analyzed and their association with treatment toxicities and outcome was evaluated. RESULTS: Genotype distribution and allele frequency were determined for SLC19A1 G80A, MTHFR C677T and A1298C, TYMS 28bp copy number variation, SLCO1B1 T521C, DHFR C-1610G/T, DHFR C-680A, DHFR A-317G and DHFR 19bp indel...
September 5, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28813770/point-counterpoint-slco1b1-genotyping-for-statins
#13
Russell A Wilke, Joseph Fanciullo
No abstract text is available yet for this article.
March 2017: South Dakota Medicine: the Journal of the South Dakota State Medical Association
https://www.readbyqxmd.com/read/28812116/slco1b1-521t%C3%A2-%C3%A2-c-polymorphism-associated-with-rosuvastatin-induced-myotoxicity-in-chinese-coronary-artery-disease-patients-a-nested-case-control-study
#14
Ju-E Liu, Xiao-Ying Liu, Sheng Chen, Yan Zhang, Li-Yun Cai, Min Yang, Wei-Hua Lai, Bin Ren, Shi-Long Zhong
PURPOSE: This nested case-control study aimed to evaluate the association of candidate genetic variants with statin-induced myotoxicity in Chinese patients with coronary artery disease (CAD). METHODS: One hundred forty-eight Chinese patients experiencing statin-induced myotoxicity were included in our study, and 255 patients without muscular side effects served as controls. Five SNPs in CYP3A5, SLCO1B1, and APOE were genotyped. The effect of genetic variants on statin-induced myotoxicity was assessed...
November 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28792790/recent-developments-and-future-directions-for-the-use-of-pharmacogenomics-in-cardiovascular-disease-treatments
#15
REVIEW
Elliot Berinstein, Andrew Levy
Cardiovascular disease is still the leading cause of death worldwide. There are many environmental and genetic factors that play a role in the development of cardiovascular disease. The treatment of cardiovascular disease is beginning to move in the direction of personalized medicine by using biomarkers from the patient's genome to design more effective treatment plans. Pharmacogenomics have already uncovered many links between genetic variation and response of many different drugs. Areas covered: This article will focus on the main polymorphisms that impact the risk of adverse effects and response efficacy of statins, clopidogrel, aspirin, β-blockers, warfarin dalcetrapib and vitamin E...
September 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28771594/patients-experiencing-statin-induced-myalgia-exhibit-a-unique-program-of-skeletal-muscle-gene-expression-following-statin-re-challenge
#16
Marshall B Elam, Gipsy Majumdar, Khyobeni Mozhui, Ivan C Gerling, Santiago R Vera, Hannah Fish-Trotter, Robert W Williams, Richard D Childress, Rajendra Raghow
Statins, the 3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase inhibitors, are widely prescribed for treatment of hypercholesterolemia. Although statins are generally well tolerated, up to ten percent of statin-treated patients experience myalgia symptoms, defined as muscle pain without elevated creatinine phosphokinase (CPK) levels. Myalgia is the most frequent reason for discontinuation of statin therapy. The mechanisms underlying statin myalgia are not clearly understood. To elucidate changes in gene expression associated with statin myalgia, we compared profiles of gene expression in skeletal muscle biopsies from patients with statin myalgia who were undergoing statin re-challenge (cases) versus those of statin-tolerant controls...
2017: PloS One
https://www.readbyqxmd.com/read/28718515/impact-of-single-nucleotide-polymorphisms-on-plasma-concentrations-of-efavirenz-and-lopinavir-ritonavir-in-chinese-children-infected-with-the-human-immunodeficiency-virus
#17
Xia Liu, Qing Ma, Yan Zhao, Weiwei Mu, Xin Sun, Yuewu Cheng, Huiping Zhang, Ye Ma, Fujie Zhang
Single nucleotide polymorphisms (SNPs) in the genes that encode the cytochrome P450 (CYP) drug metabolizing enzymes and drug transporters have been reported to influence antiretroviral drug pharmacokinetics. Although primarily metabolized by CYP2B6 and -3A, efavirenz (EFV) and lopinavir/ritonavir (LPV/r) are substrates of P-glycoprotein and the solute carrier organic (SLCO) anion transporter, respectively. We investigated the association between SNPs and efavirenz (EFV) or lopinavir/ritonavir (LPV/r) concentrations in Chinese children infected with the human immunodeficiency virus (HIV)...
September 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28653144/explaining-ethnic-variability-of-transporter-substrate-pharmacokinetics-in-healthy-asian-and-caucasian-subjects-with-allele-frequencies-of-oatp1b1-and-bcrp-a-mechanistic-modeling-analysis
#18
Rui Li, Hugh A Barton
BACKGROUND: Ethnic variability in the pharmacokinetics of organic anion transporting polypeptide (OATP) 1B1 substrates has been observed, but its basis is unclear. A previous study hypothesizes that, without applying an intrinsic ethnic variability in transporter activity, allele frequencies of transporters cannot explain observed ethnic variability in pharmacokinetics. However, this hypothesis contradicts the data collected from compounds that are OATP1B1 substrates but not breast cancer resistance protein (BCRP) substrates...
June 26, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28627804/the-effect-of-genetic-polymorphisms-in-slco2b1-on-the-lipid-lowering-efficacy-of-rosuvastatin-in-healthy-adults-with-elevated-low-density-lipoprotein
#19
Tae-Eun Kim, Dongseong Shin, Namyi Gu, Byung Hwa Jung, Jayoun Kim, Young Min Cho, Kyung-Sang Yu, Joo-Youn Cho
Rosuvastatin is an HMG-CoA reductase inhibitor widely used for treating hypercholesterolaemia. We investigated whether genetic polymorphisms in solute carrier organic anion transporter 2B1 (SLCO2B1) affect the lipid-lowering effect of rosuvastatin in healthy adults with elevated low-density lipoprotein (LDL). This study included 18 volunteers with LDL levels above 130 mg/dL. Rosuvastatin (20 mg) was administered once a day for 8 weeks. Blood samples were drawn before and after the 8-week treatment to measure changes in lipid levels...
June 19, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28594304/role-of-vitamin-d-pathway-gene-polymorphisms-on-rifampicin-plasma-and-intracellular-pharmacokinetics
#20
Sarah Allegra, Giovanna Fatiguso, Andrea Calcagno, Lorena Baietto, Ilaria Motta, Fabio Favata, Jessica Cusato, Stefano Bonora, Giovanni Di Perri, Antonio D'Avolio
AIM: We retrospectively evaluate the pharmacogenetic role of single nucleotide polymorphisms involved in rifampicin transport (SLCO1B1, MDR1 and PXR genes) and vitamin D (VDR, CYP24A1 and CYP27B1 genes) metabolism and activity on drug plasma and intracellular concentrations. PATIENTS & METHODS: Rifampicin Cmax and Ctrough were measured at weeks 2 and 4 using Ultra-Performance Liquid Chromatography-tandem mass spectroscopy methods. Allelic discrimination was performed by real-time polymerase chain reaction...
June 8, 2017: Pharmacogenomics
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