keyword
https://read.qxmd.com/read/37328288/association-between-6-thioguanine-nucleotide-levels-and-preventing-production-of-antibodies-to-infliximab-in-patients-with-inflammatory-bowel-disease
#21
JOURNAL ARTICLE
Jennifer Phillips, Sam Leary, Jonathan Tyrrell-Price
OBJECTIVE: Combination therapy with infliximab and a thiopurine has been shown to be more effective than monotherapy in patients with inflammatory bowel disease (IBD). The therapeutic efficacy of thiopurines is correlated with 6-thioguanine (6-TGN) levels between 235 and 450 pmol/8×108 erythrocytes. The primary aim of the study was to investigate the association between 6-TGN levels and inhibition prevention of the production of antibodies to infliximab (ATI). DESIGN: We performed a retrospective review of the medical records of patients being treated with infliximab for IBD at University Hospitals Bristol NHS Foundation Trust...
June 2023: BMJ Open Gastroenterology
https://read.qxmd.com/read/37218386/azathioprine-induced-vanishing-bile-duct-syndrome-the-value-of-early-thiopurine-metabolism-assessment
#22
Laurent Chouchana, Benoit Terris, Philippe Sogni, Jean-Marc Treluyer, Nathalie Costedoat-Chalumeau, Marie-Anne Loriot
About 15% to 28% of patients treated with thiopurines experienced adverse drug reactions, such as haematological and hepatic toxicities. Some of these related to the polymorphic activity of the thiopurine S-methyltransferase (TPMT), the key detoxifying enzyme of thiopurine metabolism. We report here a case of thiopurine-induced ductopenia with a comprehensive pharmacological analysis on thiopurine metabolism. A 34-year-old woman, with a medical history of severe systemic lupus erythematosus with recent introduction of azathioprine therapy, presented with mild fluctuating transaminase blood levels consistent with a hepatocellular pattern, which evolved to a cholestatic pattern over the next weeks...
May 22, 2023: British Journal of Clinical Pharmacology
https://read.qxmd.com/read/36986472/impact-of-duodenal-pathology-on-oral-drug-bioavailability-and-disease-outcomes-in-pediatric-crohn-s-disease
#23
JOURNAL ARTICLE
Rebecca Casini, Carrie A Vyhlidal, Julia M Bracken, Ashley K Sherman, Atif Ahmed, Vivekanand Singh, Veronica Williams, Valentina Shakhnovich
BACKGROUND: Crohn's disease with upper gastrointestinal tract involvement occurs more often in children than adults and has the potential to interfere with oral drug absorption. We aimed to compare disease outcomes in children receiving oral azathioprine for the treatment of Crohn's disease with (DP) and without (NDP) duodenal pathology at diagnosis. METHODS: Duodenal villous length, body mass index (BMI), and laboratory studies were compared in DP vs. NDP during the first year post-diagnosis, using parametric/nonparametric tests and regression analysis (SAS v9...
February 28, 2023: Pharmaceuticals
https://read.qxmd.com/read/36908869/-itpa-polymorphisms-and-the-incidence-of-toxicities-in-children-with-acute-lymphoblastic-leukemia
#24
JOURNAL ARTICLE
Patpetra Svasdisant, Waraporn Glomglao, Preeyanun Siraprapapat, Wiyakan Inthararujikul, Kalaya Tachavanich, Chetsada Boonthimat, Sakkarin Ardsiri, Kochpinchon Chansing, Suwimon Sriprach, Sasima Tongsai, Phakatip Sinlapamongkolkul, Kleebsabai Sanpakit, Jassada Buaboonnam
BACKGROUND: 6-Mercaptopurine (6-MP), a thiopurine agent, is a essential medication for treating pediatric acute lymphoblastic leukemia (ALL). However, its side effects of neutropenia and hepatotoxicity might interrupt treatment, resulting in poor outcomes. Inosine triphosphate pyrophosphatase ( ITPA ), an enzyme in the thiopurine pathway, may prevent the accumulation of toxic thiopurine metabolites. Studies on ITPA and thiopurine-associated toxicities are scarce. METHODS: This study retrospectively investigated 1- to 15-year-old children with ALL who received 6-MP during the maintenance phase of treatment between 2000 and 2020...
2023: Mediterranean Journal of Hematology and Infectious Diseases
https://read.qxmd.com/read/36847130/mercaptopurine-for-the-treatment-of-ulcerative-colitis-a-randomised-placebo-controlled-trial
#25
JOURNAL ARTICLE
Mark Löwenberg, Adriaan Volkers, Sara van Gennep, Aart Mookhoek, Nahid Montazeri, Esmé Clasquin, Marjolijn Duijvestein, Adriaan van Bodegraven, Svend Rietdijk, Jeroen Jansen, Dirk van Asseldonk, Esmerij van der Zanden, Marcel Dijkgraaf, Rachel West, Nanne de Boer, Geert D'Haens
BACKGROUND AND AIMS: Scepticism about the efficacy of thiopurines for ulcerative colitis (UC) is rising.This study aimed to evaluate mercaptopurine treatment for UC. METHODS: In this prospective, randomised, double-blind, placebo-controlled trial, patients with active UC, despite treatment with 5-aminosalicylates (5-ASA), were randomised for therapeutic drug monitoring (TDM)-guided mercaptopurine treatment or placebo for 52 weeks. Corticosteroids were given in the first eight weeks and 5-ASA was continued...
February 27, 2023: Journal of Crohn's & Colitis
https://read.qxmd.com/read/36788656/humoral-immune-response-to-sars-cov-2-vaccination-in-patients-with-inflammatory-bowel-disease-on-immunosuppressive-medication-association-to-serum-drug-levels-and-disease-type
#26
JOURNAL ARTICLE
Kristin Kaasen Jørgensen, Marte Lie Høivik, Adity Chopra, Jūratė Šaltytė Benth, Petr Ricanek, Prof Bjørn Moum, Ingrid Jyssum, Nils Bolstad, David John Warren, Prof John T Vaage, Prof Ludvig A Munthe, Prof Knut E A Lundin, Karoline Anisdahl, Silje Watterdal Syversen, Guro Løvik Goll, Fridtjof Lund-Johansen, Asle W Medhus, Prof Jørgen Jahnsen
OBJECTIVES: Immune responses following SARS-CoV-2 vaccination in patients with inflammatory bowel disease (IBD) are not well characterized. The aims of this study were to explore the serological response associated with IBD, and immunosuppressive medications including serum concentrations of biologics and thiopurine metabolites. MATERIALS AND METHODS: This prospective, observational study included adult patients with ulcerative colitis (UC) and Crohn's disease (CD), and healthy controls...
February 14, 2023: Scandinavian Journal of Gastroenterology
https://read.qxmd.com/read/36742181/prps2-mutations-drive-acute-lymphoblastic-leukemia-relapse-through-influencing-prps1-2-hexamer-stability
#27
JOURNAL ARTICLE
Lili Song, Peifeng Li, Huiying Sun, Lixia Ding, Jing Wang, Benshang Li, Bin-Bing S Zhou, Haizhong Feng, Yanxin Li
Tumor relapse is the major cause of treatment failure in childhood acute lymphoblastic leukemia (ALL), yet the underlying mechanisms are still elusive. Here, we demonstrate that phosphoribosyl pyrophosphate synthetase 2 (PRPS2 ) mutations drive ALL relapse through influencing PRPS1/2 hexamer stability. Ultra-deep sequencing was performed to identify PRPS2 mutations in ALL samples. The effects of PRPS2 mutations on cell survival, cell apoptosis, and drug resistance were evaluated. In vitro PRPS2 enzyme activity and ADP/GDP feedback inhibition of PRPS enzyme activity were assessed...
January 2023: Blood Sci
https://read.qxmd.com/read/36718008/investigation-of-the-association-between-the-itpa-gene-94c-a-gene-sequence-variant-and-liver-transplant-rejection-in-iranian-liver-transplant-recipients
#28
JOURNAL ARTICLE
Mozhdeh Heidari, Marzieh Khalili, Seyed Ali Malek Hosseini, Bita Geramizadeh, Ali Reza Shamsaefar, Fardin Balouchi, Mohammad Hossein Karimi
OBJECTIVES: Inosine triphosphate pyrophosphatase is an enzyme encoded by the ITPA gene and functions to prevent the incorporation of thiopurine nucleotides into DNA and RNA. Thiopurine drug metabolites such as azathioprine and 6-mercaptopurine have been included in the lists of inosine triphosphate pyrophosphatase substrates. Inosine triphosphatase gene alterations are other pharmacogenetic sequence variants possibly involved in thiopurine metabolism. This study aimed to evaluate the possible association between ITPA 94C>A gene sequence variant (C-to-A substitution at nucleotide 94) in liver transplant recipients...
December 2022: Experimental and Clinical Transplantation
https://read.qxmd.com/read/36634565/the-gut-microbiota-and-metabolome-are-associated-with-diminished-covid-19-vaccine-induced-antibody-responses-in-immunosuppressed-inflammatory-bowel-disease-patients
#29
JOURNAL ARTICLE
James L Alexander, Benjamin H Mullish, Nathan P Danckert, Zhigang Liu, Marton L Olbei, Aamir Saifuddin, Melissa Torkizadeh, Hajir Ibraheim, Jesús Miguéns Blanco, Lauren A Roberts, Claire M Bewshea, Rachel Nice, Simeng Lin, Hemanth Prabhudev, Caroline Sands, Verena Horneffer-van der Sluis, Matthew Lewis, Shaji Sebastian, Charlie W Lees, Julian P Teare, Ailsa Hart, James R Goodhand, Nicholas A Kennedy, Tamas Korcsmaros, Julian R Marchesi, Tariq Ahmad, Nick Powell
BACKGROUND: Patients with inflammatory bowel disease (IBD) treated with anti-TNF therapy exhibit attenuated humoral immune responses to vaccination against SARS-CoV-2. The gut microbiota and its functional metabolic output, which are perturbed in IBD, play an important role in shaping host immune responses. We explored whether the gut microbiota and metabolome could explain variation in anti-SARS-CoV-2 vaccination responses in immunosuppressed IBD patients. METHODS: Faecal and serum samples were prospectively collected from infliximab-treated patients with IBD in the CLARITY-IBD study undergoing vaccination against SARS-CoV-2...
February 2023: EBioMedicine
https://read.qxmd.com/read/36557210/a-validated-hplc-diode-array-detection-method-for-therapeutic-drug-monitoring-of-thiopurines-in-pediatric-patients-from-bench-to-bedside
#30
JOURNAL ARTICLE
Martina Franzin, Debora Curci, Marianna Lucafò, Matteo Bramuzzo, Marco Rabusin, Antonella Fabretto, Riccardo Addobbati, Gabriele Stocco, Giuliana Decorti
Thiopurine drugs are part of the therapeutic armamentarium for pediatric patients suffering from inflammatory bowel disease (IBD) and acute lymphoblastic leukemia (ALL). The therapeutic drug monitoring of these drugs, consisting of measurements of the thiopurine metabolites thioguanine nucleotides (TGN) and methylmercaptopurine nucleotides (MMPN) are used to optimize the effectiveness of treatment and prevent adverse effects. In this context, we developed and validated a high-performance liquid chromatography-diode array detection (HPLC-DAD) method for the simultaneous quantification of thiopurine metabolites according to the most recent International Council for Harmonisation (ICH) guidelines...
November 24, 2022: Metabolites
https://read.qxmd.com/read/36462311/dna-methylation-of-the-tpmt-gene-and-azathioprine-pharmacokinetics-in-children-with-very-early-onset-inflammatory-bowel-disease
#31
JOURNAL ARTICLE
Davide Selvestrel, Gabriele Stocco, Marina Aloi, Serena Arrigo, Sabrina Cardile, Erika Cecchin, Mauro Congia, Debora Curci, Simona Gatti, Francesco Graziano, Carl D Langefeld, Marianna Lucafò, Stefano Martelossi, Massimo Martinelli, Sofia Pagarin, Luca Scarallo, Elisabetta Francesca Stacul, Caterina Strisciuglio, Susan Thompson, Giovanna Zuin, Giuliana Decorti, Matteo Bramuzzo
BACKGROUND: Thiopurine methyltransferase (TPMT) is a crucial enzyme for azathioprine biotransformation and its activity is higher in very early onset inflammatory bowel disease (VEO-IBD) patients than in adolescents with IBD (aIBD). AIMS: The aims of this pharmacoepigenetic study were to evaluate differences in peripheral blood DNA methylation of the TPMT gene and in azathioprine pharmacokinetics in patients with VEO-IBD compared to aIBD. METHODS: The association of age with whole genome DNA methylation profile was evaluated in a pilot group of patients and confirmed by a meta-analysis on 3 cohorts of patients available on the public functional genomics data repository...
November 30, 2022: Biomedicine & Pharmacotherapy
https://read.qxmd.com/read/36262537/clinical-utility-of-thiopurine-metabolite-monitoring-in-inflammatory-bowel-disease-and-its-impact-on-healthcare-utilization-in-singapore
#32
JOURNAL ARTICLE
Jia Qi Yeo, Hua Heng McVin Cheen, Amanda Wong, Teong Guan Lim, Balram Chowbay, Wai Fook Leong, Chunyan Wang, Ennaliza Salazar, Webber Pak Wo Chan, San Choon Kong, Wan Chee Ong
Background and Aim: Thiopurines are recommended for maintenance of steroid-free remission (SFR) in inflammatory bowel disease (IBD). Thiopurine metabolite monitoring (MM) is increasingly used in the West but remains novel in Singapore, with limited information on its therapeutic and economic benefits. Hence, this study aims to investigate MM's clinical utility and its impact on healthcare resource utilization in Singaporean IBD patients. Methods: A retrospective observational study was conducted at Singapore General Hospital outpatient IBD Centre...
October 2022: JGH Open: An Open Access Journal of Gastroenterology and Hepatology
https://read.qxmd.com/read/36242689/low-dose-azathioprine-in-combination-with-allopurinol-the-past-present-and-future-of-this-useful-duo
#33
REVIEW
Alexander Keith Turbayne, Miles Patrick Sparrow
The inflammatory bowel diseases (IBD) are complex immune-mediated inflammatory diseases that are associated with significant morbidity around the world. As our understanding of IBD, and other immune-mediated inflammatory diseases, advances the number of therapeutic targets has increased which has rapidly driven the development and introduction of new therapies. While these new therapies have shown promise they come with the significant drawback of high costs. For many IBD patients around the world the cost of newer therapies is prohibitive which means treating clinicians often need to turn to optimising simpler, older, and inexpensive medications...
December 2022: Digestive Diseases and Sciences
https://read.qxmd.com/read/36238550/optimizing-thiopurine-therapy-in-children-with-acute-lymphoblastic-leukemia-a-promising-mint-sequencing-strategy-and-therapeutic-dna-tg-monitoring
#34
REVIEW
Hong-Li Guo, Yue-Tao Zhao, Wei-Jun Wang, Na Dong, Ya-Hui Hu, Yuan-Yuan Zhang, Feng Chen, Li Zhou, Tao Li
Thiopurines, including thioguanine (TG), 6-mercaptopurine (6-MP), and azathioprine (AZA), are extensively used in clinical practice in children with acute lymphoblastic leukemia (ALL) and inflammatory bowel diseases. However, the common adverse effects caused by myelosuppression and hepatotoxicity limit their application. Metabolizing enzymes such as thiopurine S-methyltransferase (TPMT), nudix hydrolase 15 (NUDT15), inosine triphosphate pyrophosphohydrolase (ITPA), and drug transporters like multidrug resistance-associated protein 4 (MRP4) have been reported to mediate the metabolism and transportation of thiopurine drugs...
2022: Frontiers in Pharmacology
https://read.qxmd.com/read/36233187/improved-hplc-quantification-of-6-mercaptopurine-metabolites-in-red-blood-cells-monitoring-data-and-literature-analysis
#35
JOURNAL ARTICLE
Tiphaine Adam de Beaumais, Yves Medard, Océane Amblard, Lauriane Goldwirt, Mathieu Simonin, Christine Martinez Vinson, Arnaud Petit, Evelyne Jacqz-Aigrain
Thiopurine drugs azathioprine (AZA) and 6-mercaptopurine (6-MP) are used extensively in pediatric and adult patients with inflammatory and neoplastic diseases. They are metabolized to 6-thioguanine nucleotides (6-TGN) or to 6-methyl-mercaptopurine nucleotides (6-MMPN). The balance between 6-TGN and 6-MMPN is highly variable and monitoring is recommended, but its benefit in outcome gives rise to conflicting results, potentially increased by differences in quantifying 6-MP metabolism. Our aim was to report (1) the HPLC-UV procedure used in our laboratory to quantify red blood cells (RBCs) with 6-TGN and 6-MMPN (as its derivate: 6-MMP(d)) in patients treated with thiopurines and (2) additional tests, sometimes confirmatory, to improve method standardization...
October 6, 2022: International Journal of Molecular Sciences
https://read.qxmd.com/read/36210828/-tpmt-and-nudt15-testing-for-thiopurine-therapy-a-major-tertiary-hospital-experience-and-lessons-learned
#36
JOURNAL ARTICLE
Liuh Ling Goh, Chia Wei Lim, Khai Pang Leong, Kiat Hoe Ong
Variants in thiopurine methyltransferase ( TPMT ) and nudix hydrolase 15 ( NUDT15 ) are associated with an accumulation of cytotoxic metabolites leading to increased risk of drug-related toxicity with standard doses of thiopurine drugs. We established TPMT and NUDT15 genetic testing for clinical use and evaluated the utilization, service outcomes and potential value of multi-gene PGx testing for 210 patients that underwent pharmacogenetics (PGx) testing for thiopurine therapy with the aim to optimize service delivery for future prescribing...
2022: Frontiers in Pharmacology
https://read.qxmd.com/read/35757730/case-report-azathioprine-an-old-and-wronged-immunosuppressant
#37
Pedro R Chocair, Precil Diego Miranda de Menezes Neves, Sara Mohrbacher, Maurilio Pacheco Neto, Victor A H Sato, Érico S Oliveira, Leonardo V Barbosa, Alessandra M Bales, Fagner Pereira da Silva, Américo L Cuvello-Neto, John A Duley
Mycophenolate rapidly substituted azathioprine (AZA) in transplant immunosuppression regimens since the 1990s, when early clinical trials indicated better outcomes, although opposite results were also observed. However, none of these trials used the well-established optimization methods for AZA dosing, namely, thiopurine methyltransferase pharmacogenetics combined with monitoring of the thiopurine metabolites 6-thioguanine nucleotides (6-TGN) and 6-methylmercaptopurine (6-MMP). Resistance to optimize AZA therapy remains today in transplant therapy, despite the fact that thiopurine metabolite testing is being used by other medical disciplines with evident improvement in clinical results...
2022: Frontiers in Immunology
https://read.qxmd.com/read/35745812/the-effect-of-pregnancy-and-inflammatory-bowel-disease-on-the-pharmacokinetics-of-drugs-related-to-inflammatory-bowel-disease-a-systematic-literature-review
#38
REVIEW
Thomas K Wiersma, Marijn C Visschedijk, Nanne K de Boer, Marjolijn N Lub-de Hooge, Jelmer R Prins, Daan J Touw, Paola Mian
Due to ethical and practical reasons, a knowledge gap exists on the pharmacokinetics (PK) of inflammatory bowel disease (IBD)-related drugs in pregnant women with IBD. Before evidence-based dosing can be proposed, insight into the PK has to be gained to optimize drug therapy for both mother and fetus. This systematic review aimed to describe the effect of pregnancy and IBD on the PK of drugs used for IBD. One aminosalicylate study, two thiopurine studies and twelve studies with biologicals were included. Most drugs within these groups presented data over multiple moments before, during and after pregnancy, except for mesalazine, ustekinumab and golimumab...
June 11, 2022: Pharmaceutics
https://read.qxmd.com/read/35687221/proactive-metabolite-testing-in-patients-on-thiopurine-may-yield-long-term-clinical-benefits-in-inflammatory-bowel-disease
#39
JOURNAL ARTICLE
Alex Barnes, Soong-Yuan J Ooi, Kate D Lynch, Nina Parthasarathy, Maria Bishara, Michael Gounder, Rachel Grafton, Peta Leach, Peter Bampton, Alexandra Sechi, Watson Ng, Susan Connor, Daniel van Langenberg, Réme Mountifield, Jane M Andrews
BACKGROUND: The thiopurine medications are well established in the treatment of inflammatory bowel disease (IBD). There is significant variation in levels of toxic and therapeutic metabolites. Current data from small or short-term studies support therapeutic drug monitoring (TDM) in assessing azathioprine (AZA) and 6-mercaptopurine (6MP). TDM of thiopurines involves measurement and interpretation of metabolites 6-TGN and 6-MMPR. AIMS: This study aimed to assess long-cterm outcomes of patients on thiopurines following therapeutic drug monitoring...
June 10, 2022: Digestive Diseases and Sciences
https://read.qxmd.com/read/35662571/evaluation-of-the-maternal-and-developmental-toxicity-of-6-methylmercaptopurine-riboside-in-rats
#40
JOURNAL ARTICLE
Maria Regina Gomes-Carneiro, Rosângela Ribeiro de Carvalho, Thamyris Figueiredo do Amaral, Ana Cecilia Amado Xavier De-Oliveira, Francisco José Roma Paumgartten
Thiopurine prodrugs (azathioprine, AZA, and 6-mercaptopurine, 6MP) are embryotoxic to rodents and rabbits. Little is known about the developmental toxicity of 6-methylmercaptopurine riboside (6MMPr), a thiopurine drug metabolite that is thought to mediate its liver toxicity. A limb bud assay found that 6MMPr impairs the in vitro morphogenetic differentiation of mouse limb extremities, being more potent than 6MP in the assay. This study evaluated the embryotoxicity of 6MMPr (0, 7.5, 15, 30 mg/kg bw sc) in rats after single-dose exposure in mid organogenesis (GD10)...
August 2022: Reproductive Toxicology
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