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https://www.readbyqxmd.com/read/29777022/further-studies-to-support-the-use-of-coproporphyrin-i-and-iii-as-novel-clinical-biomarkers-for-evaluating-the-potential-for-organic-anion-transporting-polypeptide-oatp-1b1-and-oatp1b3-inhibition
#1
Hong Shen, Lisa Christopher, Yurong Lai, Jiachang Gong, Hamza Kandoussi, Samira Garonzik, Vidya Perera, Tushar Garimella, W Griffith Humphreys
In a recent study, limited to South Asian Indian subjects (n=12), coproporphyrin I and III (CPI and CPIII) demonstrated properties appropriate for an OATP1B endogenous probe (Lai et al., 2016). The current studies were conducted in healthy volunteers of mixed ethnicities, including black, white, and Hispanic subjects to better understand the utility of these biomarkers in broader populations. After oral administration with 600 mg rifampin, AUC(0-24h) values were 2.8-, 3.7- and 3.6-fold higher than predose levels for CPI and 2...
May 18, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29748863/repaglinide-irbesartan-drug-interaction-effects-of-slco1b1-polymorphism-on-repaglinide-pharmacokinetics-and-pharmacodynamics-in-chinese-population
#2
Qi Pei, Jun-Yan Liu, Ji-Ye Yin, Guo-Ping Yang, Shi-Kun Liu, Yi Zheng, Pan Xie, Cheng-Xian Guo, Mi Luo, Hong-Hao Zhou, Xi Li, Zhao-Qian Liu
PURPOSE: On account of the potential inhibition of OATP1B1 (organic anion transporting polypeptide) by angiotensin II receptor blockers (ARBs) and the effects of SLCO1B1 (solute carrier organic anion transporter family member) polymorphism, the aim of current study is to assess the impact of ARBs on the pharmacokinetics (PK) and pharmacodynamics (PD) of repaglinide in Chinese healthy volunteers with different SLCO1B1 genotypes. METHODS: The in vitro study was conducted on irbesartan, valsartan, olmesartan, and losartan by using HEK293 cells transfected with OATP1B1...
May 11, 2018: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29738412/slco1b1-genetic-variation-and-hormone-therapy-in-menopausal-women
#3
Ann M Moyer, Mariza de Andrade, Stephanie S Faubion, Ekta Kapoor, Tanda Dudenkov, Richard M Weinshilboum, Virginia M Miller
OBJECTIVE: Response to menopausal hormone therapy (MHT) shows individual variation. SLCO1B1 encodes the OATP1B1 transporter expressed in the liver that transports many endogenous substances, including estrone sulfate, from the blood into hepatocytes. This study evaluated the relationship between genetic variation in SLCO1B1 and response to MHT in women enrolled in the Kronos Early Estrogen Prevention Study (KEEPS) at Mayo Clinic, Rochester, MN. METHODS: KEEPS participants were randomized to oral conjugated equine estrogen (n = 33, oCEE), transdermal 17β-estradiol (n = 33, tE2), or placebo (n = 34) for 48 months...
May 7, 2018: Menopause: the Journal of the North American Menopause Society
https://www.readbyqxmd.com/read/29732606/influence-of-6-genetic-variants-on-the-efficacy-of-statins-in-patients-with-dyslipidemia
#4
Ruth Cano-Corres, Beatriz Candás-Estébanez, Ariadna Padró-Miquel, Marta Fanlo-Maresma, Xavier Pintó, Pedro Alía-Ramos
BACKGROUND: Patients with dyslipidemia are often treated with statins to reduce lipids and hence cardiovascular risk, but treatment response is variable, partly due to genetic factors. METHODS: We studied the influence of 6 gene variants (APOE c.526C > T (APOE2), APOE c.388T > C (APOE4), SLCO1B1 c.521T > C, CYP3A4 c.-392G > A, HMGCR c.1564-106A > G, and LPA c.3947 + 467T > C) on statin efficacy assessing 2 indicators: the percent reduction in total cholesterol (TC) and non-HDL cholesterol (non-HDL), as well as the achievement of therapeutic goals...
May 7, 2018: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/29713005/genetic-structure-of-pharmacogenetic-biomarkers-in-brazil-inferred-from-a-systematic-review-and-population-based-cohorts-a-ribef-epigen-brazil-initiative
#5
Fernanda Rodrigues-Soares, Fernanda S G Kehdy, Julia Sampaio-Coelho, Poliana X C Andrade, Carolina Céspedes-Garro, Camila Zolini, Marla M Aquino, Mauricio L Barreto, Bernardo L Horta, Maria Fernanda Lima-Costa, Alexandre C Pereira, Adrián LLerena, Eduardo Tarazona-Santos
We present allele frequencies involving 39 pharmacogenetic biomarkers studied in Brazil, and their distribution on self-reported race/color categories that: (1) involve a mix of perceptions about ancestry, morphological traits, and cultural/identity issues, being social constructs pervasively used in Brazilian society and medical studies; (2) are associated with disparities in access to health services, as well as in their representation in genetic studies, and (3), as we report here, explain a larger portion of the variance of pharmaco-allele frequencies than geography...
May 1, 2018: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29695692/-multiplex-genotyping-of-allelic-variants-of-genes-involved-in-metabolizing-antileukemic-drugs
#6
D O Fesenko, M A Avdonina, L G Gukasyan, S A Surzhikov, A V Chudinov, A S Zasedatelev, T V Nasedkina
A biochip, primer set, and genotyping protocol were developed to simultaneously address 16 single nucleotide polymorphisms in antileukemic drug metabolism genes, including TPMT, ITPA, MTHFR, SLCO1B1, SLC19A1, NR3C1, GRIA1, ASNS, MTRR, and ABCB1. The genotyping procedure included a one-round multiplex polymerase chain reaction (PCR) with simultaneous incorporation of a fluorescent label into the PCR product and subsequent hybridization on a biochip with immobilized probes. The method was used to test 65 DNA samples of leukemia patients...
March 2018: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/29683977/slco1b1-polymorphism-is-a-drug-response-predictive-marker-for-advanced-pancreatic-cancer-patients-treated-with-gemcitabine-s-1-or-gemcitabine-plus-s-1
#7
Yasunori Sato, Hideki Ueno, Tatsuya Ioka, Shinichi Ohkawa, Masafumi Ikeda, Tomotaka Shimamura, Akihito Tsuji, Yoshiaki Tsuchiya, Junji Furuse, Hiroshi Ishii, Ken Furuya, Haruo Iguchi, Yoshihiro Saito, Nahoko Kaniwa, Jun-Ichi Sawada, Hiromi Sakamoto, Akihiro Sekine, Takuji Okusaka, Teruhiko Yoshida
OBJECTIVES: The aim of this study was to evaluate the effects of single-nucleotide polymorphisms (SNPs) on advanced pancreatic cancer risk and overall survival (OS) in a candidate-gene approach. METHODS: Overall, 5438 SNPs in 219 candidate genes encoding several drug-metabolizing enzymes or transporters were analyzed. In the screening study, 3 SNPs were found associated with OS (P ≤ 0.0005). We validated these SNPs as part of the randomized phase 3 study (GEST study)...
April 19, 2018: Pancreas
https://www.readbyqxmd.com/read/29683944/slco1b1-polymorphisms-are-associated-with-drug-intolerance-in-childhood-leukemia-maintenance-therapy
#8
İrem Eldem, Duygu Yavuz, Özge Cumaoğullari, Talia İleri, Elif Ünal İnce, Mehmet Ertem, Beyza Doğanay Erdoğan, Recep Bindak, Hilal Özdağ, N Lale Şatiroğlu-Tufan, L Zümrüt Uysal
BACKGROUND: Therapy discontinuations and toxicities occur because of significant interindividual variations in 6-mercaptopurine (6-MP) and methotrexate (MTX) response during maintenance therapy of childhood acute lymphoblastic leukemia (ALL). 6-MP/MTX intolerance in some of the patients cannot be explained by thiopurine S-methyl transferase (TPMT) gene variants. In this study, we aimed to investigate candidate pharmacogenetic determinants of 6-MP and MTX intolerance in Turkish ALL children...
April 20, 2018: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29679469/influence-of-transporter-polymorphisms-on-drug-disposition-and-response-a-perspective-from-the-international-transporter-consortium
#9
Sook Wah Yee, Deanna J Brackman, Elizabeth A Ennis, Yuichi Sugiyama, Landry K Kamdem, Rebecca Blanchard, Aleksandra Galetin, Lei Zhang, Kathleen M Giacomini
Advances in genomic technologies have led to a wealth of information identifying genetic polymorphisms in membrane transporters, specifically how these polymorphisms affect drug disposition and response. This review describes the current perspective of the International Transporter Consortium (ITC) on clinically important polymorphisms in membrane transporters. ITC suggests that in addition to previously recommended polymorphisms in ABCG2 (BCRP) and SLCO1B1 (OATP1B1), polymorphisms in the emerging transporter, SLC22A1 (OCT1), be considered during drug development...
April 21, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29575099/lack-of-association-between-slco1b1-polymorphisms-and-lipid-lowering-response-to-simvastatin-therapy-in-thai-hypercholesterolaemic-patients
#10
N Kaewboonlert, W Thitisopee, W Sirintronsopon, S Porntadavity, N Jeenduang
WHAT IS KNOWN: SLCO1B1 polymorphisms have been reported to affect the responses to statin therapy. However, the association of these polymorphisms and lipid-lowering responses has been inconsistent. OBJECTIVE: To investigate the effect of SLCO1B1 c.388A>G, c.521T>C and g.89595T>C polymorphisms on the lipid-lowering response to simvastatin therapy in Thai hypercholesterolaemic patients. METHODS: Three hundred and 91 hypercholesterolaemic patients in Southern Thailand were enrolled and treated with simvastatin 20 or 40 mg per day...
March 25, 2018: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/29534995/statin-induced-myopathy-slco1b1-521t-c-is-associated-with-prediabetes-high-body-mass-index-and-normal-lipid-profile-in-emirati-population
#11
Maha Saber-Ayad, Shaista Manzoor, Ahmed El-Serafy, Ibrahim Mahmoud, Salah Abusnana, Nabil Sulaiman
BACKGROUND: Statin-induced myopathy has been linked to the C allele of a single nucleotide polymorphism (SNP) (rs4149056) of SLCO1B1 gene. This effect is more significant, but not restricted to simvastatin. Many studies have included European, American, African and Southeast Asian ancestries, but few were carried out on Middle Eastern population. AIM: To detect the prevalence of SLCO1B1 rs4149056 (521T>C) in Emirati population. METHOD: We recruited 282 Emiratis through the UAE National Diabetes and Lifestyle Project...
March 10, 2018: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/29524031/contribution-of-ugt1a1-genetic-polymorphisms-related-to-axitinib-pharmacokinetics-to-safety-and-efficacy-in-patients-with-renal-cell-carcinoma
#12
Ryoma Igarashi, Takamitsu Inoue, Nobuhiro Fujiyama, Norihiko Tsuchiya, Kazuyuki Numakura, Hideaki Kagaya, Mitsuru Saito, Shintaro Narita, Shigeru Satoh, Takenori Niioka, Masatomo Miura, Tomonori Habuchi
Axitinib is a potent second-line molecular-targeted agent for metastatic renal cell carcinoma (mRCC). Axitinib pharmacokinetics and its relation with genetic polymorphisms were evaluated to predict the adverse events (AEs) and efficacy of axitinib. We analyzed 46 patients with mRCC who were treated with axitinib. The plasma axitinib level was measured at 0, 2, 4, 8, and 12 h after administration (C0 , C2 , C4 , C8 , and C12 ; ng/mL) on day 7 of the treatment. Genetic polymorphisms related to axitinib pharmacokinetics, including SLCO1B1, SLCO1B3, SLCO2B1, ABCB1, ABCG2, CYP2C19, CYP3A5, and UGT1A1, were analyzed...
March 9, 2018: Medical Oncology
https://www.readbyqxmd.com/read/29517466/allelic-frequencies-of-60-pharmacogene-variants-assessed-within-a-burmese-population-residing-in-northeast-indiana-usa
#13
Carrie C Hoefer, Emily J Brick, Ann Savariar, David F Kisor, Amy Dawson, Ahmad Khatri, Brian Henriksen
AIM: The aim of this study was to investigate 60 SNPs pertaining to drug metabolism and pharmacodynamics in the Burmese refugee population in the Fort Wayne, Indiana area to better inform patient care. MATERIALS & METHODS: Sixty-two self-identified Burmese refugees were genotyped for 60 common SNPs pertaining to pharmacokinetic and pharmacodynamic pharmacogenes. The resulting allelic frequencies were compared with Ensembl's database for surrounding populations to Myanmar and America...
April 2018: Pharmacogenomics
https://www.readbyqxmd.com/read/29499902/effect-of-ugt-slco-abcb-and-abcc-polymorphisms-on-irinotecan-toxicity
#14
Sara García Gil, Ruth Ramos Díaz, Gloria Julia Nazco Casariego, Marta Llanos Muñoz, Maria Micaela Viña Romero, Braulio Martín Calero, Jose Antonio Pérez Pérez, Fernando Gutiérrez Nicolás
BACKGROUND AND OBJECTIVES: Evaluate the relationship between the presence of polymorphisms in genes involved in the pharmacodynamics of irinotecan (UGT1A, SLCO1B1, ABCB1 and ABCC2) and the safety of irinotecan in the treatment of metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Prospective observational, single-centre study of 30 months duration, which included patients diagnosed with mCRC treated with FOLFIRI was carried out. Toxicity was evaluated in each treatment cycle according to the Common Terminology Criteria for Adverse Events (CTCAE) v...
February 27, 2018: Medicina Clínica
https://www.readbyqxmd.com/read/29472495/apixaban-and-rosuvas-tatin-pharmacokinetics-in-nonalcoholic-fatty-liver-disease
#15
Rommel G Tirona, Zahra Kassam, Ruth Strapp, Mala Ramu, Catherine Zhu, Melissa Liu, Ute I Schwarz, Richard B Kim, Bandar Al-Judaibi, Melanie D Beaton
There is little known about the impact of nonalcoholic fatty liver disease (NAFLD) on drug metabolism and transport. We examined the pharmacokinetics of oral apixaban (2.5 mg) and rosuvastatin (5 mg) when administered simultaneously in subjects with magnetic resonance imaging-confirmed NAFLD ( N = 22) and healthy control subjects ( N = 12). The area under the concentration-time curve to the last sampling time (AUC0-12 ) values for apixaban were not different between control and NAFLD subjects (671 and 545 ng/ml × hour, respectively; P = 0...
May 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29469964/impact-of-slco1b1-genotype-on-pediatric-simvastatin-acid-pharmacokinetics
#16
Jonathan B Wagner, Susan Abdel-Rahman, Leon Van Haandel, Andrea Gaedigk, Roger Gaedigk, Geetha Raghuveer, Ralph Kauffman, J Steven Leeder
This study investigated the impact of allelic variation in SLCO1B1, a gene encoding for the liver-specific solute carrier organic anion transporter family member 1B1 protein (SLCO1B1), on simvastatin and simvastatin acid (SVA) systemic exposure in children and adolescents. Participants (8-20 years old) with at least 1 variant SLCO1B1 c.521T>C allele (521TC, n = 15; 521CC, n = 2) and 2 wild-type alleles (521TT, n = 15) completed a single oral dose pharmacokinetic study. At equivalent doses, SVA exposure was 6...
February 22, 2018: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29463526/elevated-plasma-moxifloxacin-concentrations-and-slco1b1-g-11187g-a-polymorphism-in-adults-with-pulmonary-tuberculosis
#17
Marc Weiner, Jon Gelfond, Teresa L Johnson-Pais, Melissa Engle, Charles A Peloquin, John L Johnson, Erin E Sizemore, William R Mac Kenzie
Moxifloxacin exhibits concentration-dependent prolongation of human QTc intervals and bactericidal activity against Mycobacterium tuberculosis However, moxifloxacin plasma concentrations are variable between patients. We evaluated whether human gene polymorphisms affect moxifloxacin plasma concentrations in tuberculosis patients from two geographic regions. We enrolled a convenience sample of 49 adults with drug-sensitive pulmonary tuberculosis from Africa and the United States enrolled in two treatment trials of moxifloxacin as part of multidrug therapy...
May 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29442027/the-effect-of-slco1b1-polymorphism-on-the-pharmacokinetics-of-atorvastatin-and-2-hydroxyatorvastatin-in-healthy-chinese-people
#18
Yaqin Wang, Yingying Tian, Peiyu Lv, Lulu Chen, Wei Luo, Xian Jing, Hui Li, Zhirong Tan, Yicheng Wang, Honghao Zhou, Dong-Sheng Ouyang
The pharmacokinetics of statins show substantial inter-subject variability. Increasing systemic exposure of statins may lead to adverse drug reactions such as myopathy. The variation in statin pharmacokinetics is partly explained by genetic factors. OATP1B1, coded by SLCO1B1 transports a large number of therapeutic drugs, such as atorvastatin. Here we investigated the effect of SLCO1B1 polymorphism on the pharmacokinetics of atorvastatin and its metabolites. Two pharmacokinetic studies were conducted in Chinese Han volunteers and 132 volunteers were enrolled in our study as 72 in trial 1 and 60 in trial 2...
June 1, 2017: Die Pharmazie
https://www.readbyqxmd.com/read/29441875/influence-of-slco1b1-polymorphisms-on-atorvastatin-efficacy-and-safety-in-macedonian-subjects
#19
K Mladenovska, A Daka Grapci, M Vavlukis, A Kapedanovska, A Eftimov, N Matevska Geshkovska, D Nebija, A J Dimovski
Atorvastatin, as 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, is a widely prescribed medication for the treatment of dyslipidemia. However, despite its clinical efficacy in reducing major cardiovascular events, a wide inter-individual variability in its response exists. Several studies in this area point to the effect of polymorphisms in the solute carrier organic anion transporter 1B1 (SLCO1B1) gene encoding the multiple organic anion-transporting polypeptide 1B1 (OATP1B1) involved in hepatic uptake of atorvastatin...
May 1, 2017: Die Pharmazie
https://www.readbyqxmd.com/read/29440451/establishing-transcriptional-signatures-to-differentiate-pxr-car-and-ahr-mediated-regulation-of-drug-metabolism-and-transport-genes-in-cryopreserved-human-hepatocytes
#20
Jamie E Moscovitz, Amit S Kalgutkar, Kelly Nulick, Nathaniel Johnson, Zhiwu Lin, Theunis C Goosen, Yan Weng
The potential for drug-drug interactions (DDIs) arising from transcriptional regulation of drug-disposition genes via activation of nuclear receptors (NRs), such as pregnane X receptor (PXR), constitutive androstane receptor (CAR), and aryl hydrocarbon receptor (AhR), remains largely unexplored, as highlighted in a recent guidance document from the European Medicines Agency. The goal of this research was to establish PXR-/CAR-/AhR-specific drug-metabolizing enzyme (DME) and transporter gene expression signatures in sandwich-cultured cryopreserved human hepatocytes using selective activators of PXR (rifampin), CAR (CITCO), and AhR (omeprazole)...
May 2018: Journal of Pharmacology and Experimental Therapeutics
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