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6-TGN

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https://www.readbyqxmd.com/read/29206869/measurements-of-6-thioguanine-nucleotide-levels-with-tpmt-and-nudt15-genotyping-in-patients-with-crohn-s-disease
#1
Ji Hyeon Lee, Tae Jun Kim, Eun Ran Kim, Sung Noh Hong, Dong Kyung Chang, Li-Hwa Choi, Hye In Woo, Soo-Youn Lee, Young-Ho Kim
The association between the 6-thioguanine nucleotide (6-TGN) level and clinical remission in Crohn's disease (CD) remains controversial. Thiopurine-induced leukopenia is a life-threatening complication of CD in Asians that was recently shown to strongly correlate with NUDT15 genetic variants. This study aimed to determine the relationship between thiopurine metabolite levels and therapeutic response, and to investigate the association of NUDT15, TPMT, and thiopurine metabolites with leukopenia in patients with CD...
2017: PloS One
https://www.readbyqxmd.com/read/29147133/allopurinol-in-combination-with-thiopurine-induces-mucosal-healing-and-improves-clinical-and-metabolic-outcomes-in-ibd
#2
Brigitte Moreau, Pierre Clement, Yves Theoret, Ernest G Seidman
Background: Thiopurines, azathioprine (AZA) and 6-mercaptopurine (6-MP) are common maintenance medications for inflammatory bowel disease (IBD). Excessive methylation via thiopurine methyltransferase (TPMT) frequently causes therapeutic failure. Allopurinol reduces excessive 6-methyl-mercaptopurine (6-MMP) while enhancing 6-thioguanine (6-TGN) levels. The aim of this study was to evaluate clinical, metabolic and endoscopic impact of allopurinol in combination with low-dose thiopurine in IBD...
November 2017: Therapeutic Advances in Gastroenterology
https://www.readbyqxmd.com/read/29145599/a-role-for-thiopurine-metabolites-in-the-synergism-between-thiopurines-and-infliximab-in-inflammatory-bowel-disease
#3
Ditte V Mogensen, Jørn Brynskov, Mark A Ainsworth, Jacob Nersting, Kjeld Schmiegelow, Casper Steenholdt
Background: Interactions between principal cytotoxic thiopurine metabolites, 6-thioguanine nucleotides (6-TGN), and infliximab (IFX) and anti-IFX antibodies (Abs) may contribute to higher effectiveness of IFX-thiopurine-combination therapy than monotherapies in inflammatory bowel disease. Methods: To examine if thiopurine metabolites influenced trough IFX and anti-IFX Abs, 89 patients previously assessed for anti-IFX Abs were included. To assess if IFX influenced thiopurine metabolites, 8 patients having responded to 12 weeks of intensified IFX at a constant thiopurine dosing were included...
November 14, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/29040228/analytical-pitfalls-of-therapeutic-drug-monitoring-of-thiopurines-in-patients-with-inflammatory-bowel-disease
#4
Melek Simsek, Berrie Meijer, Chris J J Mulder, Adriaan A van Bodegraven, Nanne K H de Boer
The use of thiopurines in the treatment of inflammatory bowel disease (IBD) can be optimized by the application of therapeutic drug monitoring. In this procedure, 6-thioguanine nucleotides (6-TGN) and 6-methylmercaptopurine (6-MMP) metabolites are monitored and related to therapeutic response and adverse events, respectively. Therapeutic drug monitoring of thiopurines, however, is hampered by several analytical limitations resulting in an impaired translation of metabolite levels to clinical outcome in IBD...
December 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28914560/thiopurine-metabolite-levels-in-patients-with-atopic-dermatitis-and-or-chronic-hand-foot-eczema-treated-with-azathioprine
#5
F M Garritsen, J van der Schaft, C A F Bruijnzeel-Koomen, R H van Schaik, M de Graaf, M P H van den Broek, M S de Bruin-Weller
BACKGROUND: Azathioprine is frequently used in severe eczema. It is converted in the liver into active metabolites, including 6-thioguanine nucleotide (6-TGN) and methylated 6-methylmercaptopurine (6-MMP). In the past, the therapeutic potential of azathioprine may have not been fully utilized. Recent investigations on inflammatory bowel disease have led to a better understanding of azathioprine metabolism and optimizing treatment. OBJECTIVE: To investigate whether measuring thiopurine metabolites in circulation can improve the effectiveness and safety of azathioprine treatment in patients with atopic dermatitis and/or chronic hand/foot eczema...
September 26, 2017: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/28903549/nudt15-variants-cause-hematopoietic-toxicity-with-low-6-tgn-levels-in-children-with-acute-lymphoblastic-leukemia
#6
Eun Sang Yi, Young Bae Choi, Rihwa Choi, Na Hee Lee, Ji Won Lee, Keon Hee Yoo, Ki Woong Sung, Soo-Youn Lee, Hong Hoe Koo
Purpose: We aimed to identify the impact of NUDT15 variants on thiopurine intolerance and 6-thioguanine nucleotide (6-TGN) levels in Korean children with acute lymphoblastic leukemia (ALL). Materials and Methods: Genotyping of NUDT15 was tested in 258 patients with ALL registered at Samsung Medical Center. Patients were classified into normal-activity (wild-type), intermediate-activity (heterozygous variant), and low-activity groups (homozygous or compound heterozygous variant)...
September 13, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28723860/higher-thioguanine-nucleotide-metabolite-levels-are-associated-with-better-long-term-outcomes-in-patients-with-inflammatory-bowel-diseases
#7
Andres J Yarur, Bilal Gondal, Ayal Hirsch, Britt Christensen, Russell D Cohen, David T Rubin
GOALS: The aim of this study was to assess whether sustained 6-thioguaninenucleotide (6-TGN) levels were associated with improved long-term outcomes in patients with inflammatory bowel diseases (IBD). BACKGROUND: Cross-sectional data have shown that thiopurine metabolites are correlated with clinical efficacy in patient receiving thiopurines for IBD but the role for serial measurements through treatment course is unclear. STUDY: We conducted a retrospective cohort study including patients with IBD on thiopurine monotherapy and had serial 6-TGN levels measured...
July 18, 2017: Journal of Clinical Gastroenterology
https://www.readbyqxmd.com/read/28679367/relationship-between-azathioprine-metabolites-and-therapeutic-efficacy-in-chinese-patients-with-neuromyelitis-optica-spectrum-disorders
#8
Xindi Li, Shenghui Mei, Xiaoqing Gong, Heng Zhou, Li Yang, Anna Zhou, Yonghong Liu, Xingang Li, Zhigang Zhao, Xinghu Zhang
BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) are demyelinating autoimmune diseases in the central nervous system (CNS) that are characterized by a high relapse rate and the presence of anti-aquaporin 4 antibodies (AQP4-IgG) in the serum. Azathioprine (AZA) is a first-line immunomodulatory drug that is widely used for the treatment of patients with NMOSD. However, the efficacy and safety of AZA vary in different individuals. METHOD: Thirty-two patients with NMOSD who regularly took AZA were enrolled in the study at Beijing Tiantan Hospital, Capital Medical University...
July 5, 2017: BMC Neurology
https://www.readbyqxmd.com/read/28650902/itpa-activity-in-adults-and-children-treated-with-or-without-azathioprine-relationship-between-tpmt-activity-thiopurine-metabolites-and-co-medications
#9
Antony Citterio-Quentin, Mustapha Moulsma, Marie-Paule Gustin, Roselyne Boulieu
BACKGROUND: The implication of inosine triphosphate pyrophosphatase (ITPA) on thiopurine drug response variability has been investigated but little data are available on its role on thiopurine metabolites. The ability of ITPA to modify the thiopurine metabolite levels is currently used to optimize azathioprine (AZA) therapy in relation to thiopurine S-methyltransferase (TPMT) activity, the aim of this study is to investigate ITPA phenotype in a large population and to evaluate the relation between ITPA and TPMT activities and thiopurine metabolites...
October 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28489727/pharmacology-of-thiopurine-therapy-in-inflammatory-bowel-disease-and-complete-blood-cell-count-outcomes-a-5-year-database-study
#10
Berrie Meijer, Abraham J Wilhelm, Chris J J Mulder, Gerd Bouma, Adriaan A van Bodegraven, Nanne K H de Boer
BACKGROUND: Thiopurines are the prerequisite for immunomodulation in inflammatory bowel disease (IBD) therapy. When administered in high (oncological) dose, thiopurine metabolites act as purine antagonists, causing DNA-strand breakage and myelotoxicity. In lower IBD dosages, the mode of action is primarily restricted to anti-inflammatory effects. Then, myelosuppression and hepatotoxicity are the most common adverse events of thiopurines. The aim of this study was to assess the effect of thiopurine metabolites on hematologic and hepatic parameters and to determine which patient characteristics are related to generation of thiopurine metabolites...
August 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28449228/azathioprine-dose-reduction-in-inflammatory-bowel-disease-patients-on-combination-therapy-an-open-label-prospective-and-randomised-clinical-trial
#11
X Roblin, G Boschetti, N Williet, S Nancey, H Marotte, A Berger, J M Phelip, L Peyrin-Biroulet, J F Colombel, E Del Tedesco, S Paul, B Flourie
BACKGROUND: Infliximab (IFX) combined with azathioprine (AZA) is more effective than IFX monotherapy in inflammatory bowel disease (IBD). AIM: To identify the AZA optimal dose that is required for efficacy when receiving combination therapy. METHODS: Patients with IBD in durable remission on combination therapy were enrolled in a 1-year, open-label, prospective trial after randomisation into three groups: AZA steady (2-2.5 mg/kg/day, n=28) vs AZA down (dose was halved 1-1...
April 27, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28333183/machine-learning-algorithms-for-objective-remission-and-clinical-outcomes-with-thiopurines
#12
Akbar K Waljee, Kay Sauder, Anand Patel, Sandeep Segar, Boang Liu, Yiwei Zhang, Ji Zhu, Ryan W Stidham, Ulysses Balis, Peter D R Higgins
Background and Aims: Big data analytics leverage patterns in data to harvest valuable information, but are rarely implemented in clinical care. Optimising thiopurine therapy for inflammatory bowel disease [IBD] has proved difficult. Current methods using 6-thioguanine nucleotide [6-TGN] metabolites have failed in randomized controlled trials [RCTs], and have not been used to predict objective remission [OR]. Our aims were to: 1) develop machine learning algorithms [MLA] using laboratory values and age to identify patients in objective remission on thiopurines; and 2) determine whether achieving algorithm-predicted objective remission resulted in fewer clinical events per year...
July 1, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28272159/outcomes-in-pediatric-autoimmune-hepatitis-and-significance-of-azathioprine-metabolites
#13
Melissa A Sheiko, Shikha S Sundaram, Kelley E Capocelli, Zhaoxing Pan, Annette M McCoy, Cara L Mack
OBJECTIVES: Autoimmune hepatitis (AIH) is a common pediatric liver disease and long-term remission is usually maintained with azathioprine (AZA). There is no consensus on the target range for AZA active metabolite 6-thioguanine (6-TGN) levels in pediatric AIH. The aim of the present study was to characterize the outcomes of pediatric patients with AIH and determine correlations between AZA dosing or 6-TGN metabolite levels and biochemical remission. METHODS: A retrospective chart review was performed and data on presentation, laboratories including AZA metabolite levels, medication use, and outcomes were collected...
July 2017: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/28175074/p428-optimizing-thiopurines-in-crohn-s-disease-low-dose-and-low-6-tgn-level-are-effective-for-maintenance-of-remission-in-asian-population
#14
R Mao, J Guo, S Ben Horin, M Chen
No abstract text is available yet for this article.
February 1, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28130685/metabolite-monitoring-to-guide-thiopurine-therapy-in-systemic-autoimmune-diseases
#15
Aurélie Chapdelaine, Anne-Marie Mansour, Yves Troyanov, David R Williamson, Maxime Doré
6-Thioguanine nucleotide (6-TGN) is the active metabolite of thiopurine drugs azathioprine and 6-mercaptopurine. 6-Methylmercaptopurine (6-MMP) is an inactive and potentially hepatotoxic metabolite. A subgroup of patients (shunters) preferentially produce 6-MMP instead of 6-TGN, therefore displaying thiopurine resistance and risk for hepatotoxicity. Outside inflammatory bowel disease literature, few data exist regarding individualized thiopurine therapy based on metabolite monitoring. This study sought to describe metabolite monitoring in patients receiving weight-based thiopurine for systemic autoimmune diseases...
June 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28045129/the-glutathione-transferase-mu-null-genotype-leads-to-lower-6-mmpr-levels-in-patients-treated-with-azathioprine-but-not-with-mercaptopurine
#16
M M T J Broekman, D R Wong, G J A Wanten, H M Roelofs, C J van Marrewijk, O H Klungel, A L M Verbeek, P M Hooymans, H-J Guchelaar, H Scheffer, L J J Derijks, M J H Coenen, D J de Jong
The conversion of azathioprine (AZA) to mercaptopurine (MP) is mediated by glutathione transferase Mu1 (GSTM1), alpha1 (GSTA1) and alpha2 (GSTA2). We designed a case-control study with data from the TOPIC trial to explore the effects of genetic variation on steady state 6-methylmercaptopurine ribonucleotide (6-MMPR) and 6-thioguanine nucleotide (6-TGN) metabolite levels. We included 199 patients with inflammatory bowel disease (126 on AZA and 73 on MP). GSTM1-null genotype carriers on AZA had two-fold lower 6-MMPR levels than AZA users carrying one or two copies of GSTM1 (2239 (1006-4587) versus 4371 (1897-7369) pmol/8 × 10(8) RBCs; P<0...
January 3, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/27604507/nudt15-polymorphisms-are-better-than-thiopurine-s-methyltransferase-as-predictor-of-risk-for-thiopurine-induced-leukopenia-in-chinese-patients-with-crohn-s-disease
#17
X Zhu, X-D Wang, K Chao, M Zhi, H Zheng, H-L Ruan, S Xin, N Ding, P-J Hu, M Huang, X Gao
BACKGROUND: Thiopurine-induced leukopenia is the most common dangerous adverse event in Asians. NUDT15 R139C was recently proposed to be a promising biomarker for leukopenia with thiopurine therapy in Asians, but this has not been replicated in the Chinese population. AIM: To investigate the influence of NUDT15 R139C, thiopurine S-methyltransferase (TPMT), 6-TGN and 6-MMPR on thiopurine-induced leukopenia in Chinese patients with Crohn's disease. METHODS: Clinical and epidemiological characteristics were reviewed from medical records...
November 2016: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27496503/determination-of-concentrations-of-azathioprine-metabolites-6-thioguanine-and-6-methylmercaptopurine-in-whole-blood-with-the-use-of-liquid-chromatography-combined-with-mass-spectrometry
#18
D Zochowska, J Zegarska, E Hryniewiecka, E Samborowska, R Jazwiec, W Tszyrsznic, A Borowiec, M Dadlez, L Paczek
BACKGROUND: 6-Mercaptopurine (6-MP) and its prodrug azathioprine (AZA) are used in many autoimmune diseases and after solid-organ transplantation. Their properties are mediated by active metabolites, 6-thioguanine nucleotides (6-TGN), and 6-methylmercaptopurine (6-MMP). The most common adverse effects are myelo- and hepato-toxicity. The aim of the study was quantification of 6-TG and 6-MMP, with the use of liquid chromatography combined with tandem mass spectrometry (LC/MS/MS) in solid-organ transplant recipients...
June 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27392985/-not-available
#19
May Fakhoury, Evelyne Jacqz-Aigrain, Tiphaine de Beaumais, Yves Médard
6-mercaptopurine, a key drug for the treatment of acute lymphoblastic leukaemia in children, is a prodrug metabolized into 6-thioguanine (6-TGN) which are the active compounds and into methylated metabolites, primary by thiopurine S-methyltransferase enzyme (TPMT). This enzyme displays important inter subject variability linked to a genetic polymorphism: when treated with standard doses of thiopurine, TPMT-deficient and heterozygous patients are at great risk for developing severe and potentially life-threatening toxicity (hematopoietic, hepatic, mucositis...
May 2010: Thérapie
https://www.readbyqxmd.com/read/27257870/usefulness-of-mean-corpuscular-volume-as-a-surrogate-marker-for-monitoring-thiopurine-treatment-in-inflammatory-bowel-disease
#20
REVIEW
Romein W G Dujardin, Berrie Meijer, Nanne K H de Boer, Geert R D'Haens, Mark Löwenberg
BACKGROUND: Thiopurines are commonly used drugs in inflammatory bowel disease. Intracellular levels of thiopurine metabolites [i.e. 6-thioguaninenucleotides (6-TGN)] are associated with efficacy and toxicity. Because 6-TGN measurement is not globally available, the mean corpuscular volume (MCV) has been proposed as a surrogate marker for monitoring thiopurine therapy. AIMS: To analyze the relationship between MCV and efficacy of thiopurines, defined as either response to therapy or 6-TGN levels...
September 2016: European Journal of Gastroenterology & Hepatology
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