331 results match your criteria Azathioprine Metabolism and TPMT


[Frequency of serious adverse events of thiopurine treatment in normal thiopurine S-methyltransferase genotype children with inflammatory bowel disease].

Authors:
András Tárnok

Orv Hetil 2019 Feb;160(5):179-185

Gyermekgyógyászati Klinika, Pécsi Tudományegyetem, Általános Orvostudományi Kar Pécs, József A. u. 7., 7623.

Introduction: Genetic polymorphism of thiopurine S-methyltransferase, the key enzyme in metabolism of thiopurines (azathioprine and 6-mercaptopurine) used in the treatment of inflammatory bowel disease, results in different enzyme activities. Decreased enzyme activity causes myelosuppression whereas abnormally high activity results in hepatotoxicity at standard thiopurine doses. Four allele variants (TMPT*2, TMPT*3A, TPMT*3B and TPMT*3C) account for decreased activity in more than 95% of cases. Read More

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http://dx.doi.org/10.1556/650.2019.31277DOI Listing
February 2019
1 Read

Thiopurine S-methyltransferase (TPMT) Mutation Prevalence and Myelosuppression Frequency in North Indian Patients with Autoimmune Disorders.

J Assoc Physicians India 2018 May;66(5):39-44

Sir Ganga Ram Hospital, New Delhi.

Background: For many years, azathioprine and its active metabolite 6-merceptopurine are used as immunosuppressants for treatment of autoimmune disorders. However, azathioprine has low therapeutic index with myelosuppression as its predominant toxicity which is linked with thiopurine S-methyltransferase (TPMT) enzyme activity, which is involved in drug metabolism. TPMT activity is controlled by variants in TPMT gene. Read More

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May 2018
6 Reads

Red Blood cell IMPDH activity in adults and children with or without azathioprine: Relationship between thiopurine metabolites, ITPA and TPMT activities.

Basic Clin Pharmacol Toxicol 2018 Nov 19. Epub 2018 Nov 19.

Clinical Pharmacy, Pharmacokinetics and Drug Evaluation, Université de Lyon, Université Lyon 1, France.

Inosine monophosphate dehydrogenase (IMPDH) is considered as the limiting enzyme of thiopurine metabolism for the formation of 6-thioguanine nucleotides (6-TGN). No data are available on the influence of RBC IMPDH activity on the metabolism of thiopurine drugs in individuals with IBD. The aims of this study were as follows: (a) to carry out a phenotypic study of RBC IMPDH activity in adults and children treated or not with azathioprine (AZA) for autoimmune diseases, and (b) to investigate the relationship between the activities of IMPDH, thiopurine metabolites, inosine triphosphatase (ITPA) and thiopurine methyltransferase (TPMT). Read More

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http://dx.doi.org/10.1111/bcpt.13176DOI Listing
November 2018
13 Reads

Thiopurine Methyltransferase genetic polymorphisms and activity and metabolic products of azathioprine in patients with inflammatory bowel disease.

Endocr Metab Immune Disord Drug Targets 2018 Nov 19. Epub 2018 Nov 19.

Golestan Research Center of Gasteroenterolgy and Hepatology, Golestan University of Medical Sciences, Gorgan, Golestan Province. Iran.

Background: Thiopurine S-methyltransferase (TPMT) is a cytoplasmic enzyme that catalyzes thiopurine drugs, such as 6-mercaptopurine, 6-thioguanine, and azathioprine. There is a correlation between thiopurine drug metabolism, response, and toxicity and genetic polymorphism of TPMT. The aim of this study is to assess TPMT genetic polymorphisms activity and metabolic products of AZA in patients with IBD. Read More

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http://dx.doi.org/10.2174/1871530318666181119153522DOI Listing
November 2018
10 Reads

Neutropenia related to an azathioprine metabolic disorder induced by an inosine triphosphate pyrophosphohydrolase (ITPA) gene mutation in a patient with PR3-ANCA-positive microscopic polyangiitis
.

Clin Nephrol 2018 Nov;90(5):363-369

A 68-year-old Japanese man was monitored for chronic kidney disease (CKD), with unknown primary disease starting in 2014. His serum creatinine (sCr) was stable at ~ 2.5 mg/dL for ~ 2 years. Read More

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http://dx.doi.org/10.5414/CN109383DOI Listing
November 2018
18 Reads

Severe thiopurine-induced leukocytopenia and hair loss in Japanese patients with defective NUDT15 variant: Retrospective case-control study.

J Dermatol 2018 Oct 13;45(10):1160-1165. Epub 2018 Aug 13.

Department of Dermatology, Asahikawa Medical University, Asahikawa, Japan.

Azathioprine (AZA)-metabolizing enzyme gene polymorphism is strongly related to thiopurine-induced leukocytopenia, which has not been well recognized in dermatological practice. We tried to see whether NUDT15 gene polymorphism can be the most susceptible genetic factor for AZA toxicity and the gene screening is beneficial to avoid the adverse events of AZA for the treatment of skin diseases. A retrospective study was carried out on 15 adult Japanese patients who were treated with AZA. Read More

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http://dx.doi.org/10.1111/1346-8138.14588DOI Listing
October 2018
12 Reads

Azathioprine-induced pancytopenia with normal TPMT activity presenting with HSV oral ulcers.

BMJ Case Rep 2018 Jul 11;2018. Epub 2018 Jul 11.

Department of Medicine, George Washington University, Washington, District of Columbia, USA.

A 65-year-old man with treatment-resistant psoriatic arthritis, hypertension, dyslipidaemia and benign prostatic hyperplasia (BPH) presented with herpes simplex virus (HSV) oral ulcers and a recent 15 lb weight loss due to reduced consumption. Five weeks previously, his methotrexate was tapered and he had begun taking azathioprine. The patient's thiopurine S-methyltransferase (TPMT) activity level was normal prior to starting azathioprine. Read More

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http://dx.doi.org/10.1136/bcr-2018-225209DOI Listing
July 2018
5 Reads

Association Between Thiopurine S-Methyltransferase () Genetic Variants and Infection in Pediatric Heart Transplant Recipients Treated With Azathioprine: A Multi-Institutional Analysis.

J Pediatr Pharmacol Ther 2018 Mar-Apr;23(2):106-110

Objectives: Bone marrow suppression is a common adverse effect of the immunosuppressive drug azathioprine. Polymorphisms in the gene encoding thiopurine -methyltransferase (TPMT) can alter the metabolism of azathioprine, resulting in marrow toxicity and life-threatening infection. In a multicenter cohort of pediatric heart transplant (HT) recipients, we determined the frequency of genetic variation and assessed whether azathioprine-treated recipients with variants were at increased risk of infection. Read More

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http://dx.doi.org/10.5863/1551-6776-23.2.106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5916437PMC
May 2018
6 Reads

NUDT15 R139C variation increases the risk of azathioprine-induced toxicity in Chinese subjects: Case report and literature review.

Medicine (Baltimore) 2018 Apr;97(17):e0301

Department of Pharmacy, The Affiliated Drum Tower Hospital, Nanjing University Medical School.

Introduction: Azathioprine (AZA) is widely used as an immunosuppressive agent, and its efficacy has been recommended by many clinical studies. However, leukopenia, the most common toxicity, still restricts its clinical applications. Recent studies found that NUDT15 R139C polymorphism is strongly associated with AZA-induced leukopenia in Koreans. Read More

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http://dx.doi.org/10.1097/MD.0000000000010301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5944482PMC
April 2018
6 Reads

[Genetic polymorphisms of thiopurine methyltransferase and incidence of adverse events in patients with medical indication of azathioprine].

Medicina (B Aires) 2018 ;78(2):65-70

Servicio de Inmunología, Instituto de Investigaciones Médicas (IDIM) Alfredo Lanari, Facultad de Medicina, Universidad de Buenos Aires, Argentina.

Azathioprine is a thiopurine which has a narrow therapeutic index and marked hematological and hepatic toxicity. Thiopurine s-methyltransferase is an enzyme involved in the metabolism of thiopurines. Mutations in the gene that encodes the enzyme may augment the risk of adverse events. Read More

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February 2019
2 Reads

Thiopurine methyltransferase genotype and activity cannot predict outcomes of azathioprine maintenance therapy for antineutrophil cytoplasmic antibody associated vasculitis: A retrospective cohort study.

PLoS One 2018 9;13(4):e0195524. Epub 2018 Apr 9.

Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Objective: Azathioprine is a widely used immunosuppressive drug. Genetic polymorphisms and activity of the enzyme thiopurine methyltransferase (TPMT) have been associated with azathioprine efficacy and toxicity in several populations. We investigated whether these associations also exist for ANCA associated vasculitis (AAV) patients, who receive azathioprine maintenance therapy after remission induction with cyclophosphamide. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0195524PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5890988PMC
July 2018
4 Reads

Comparison of and polymorphisms in Chinese patients with inflammatory bowel disease.

World J Gastroenterol 2018 Feb;24(8):941-948

Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China.

Aim: To observe gene polymorphisms of and , and compare their predictive value for azathioprine (AZA)-induced leukopenia in inflammatory bowel disease (IBD).

Methods: This study enrolled 219 patients diagnosed with IBD in Xiangya Hospital, Central South University, Changsha, China from February 2016 to November 2017. Peripheral blood of all patients was collected to detect their genotypes of and by pyrosequencing at the Department of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Xiangya Hospital. Read More

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http://dx.doi.org/10.3748/wjg.v24.i8.941DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5829157PMC
February 2018
7 Reads

Effect of genetic polymorphisms of azathioprine-metabolizing enzymes on response to rheumatoid arthritis treatment.

Pharmazie 2017 Jan;72(1):22-28

Azathioprine (AZA) is increasingly being prescribed to rheumatoid arthritis (RA) patients. Following oral administration, AZA is converted into its active form. Inflammatory bowel disease (IBD) and systemic lupus erythematosus (SLE) patients with low thiopurine (S)-methyltransferase (TPMT) activity tend to respond well to AZA therapy. Read More

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http://dx.doi.org/10.1691/ph.2017.6799DOI Listing
January 2017
2 Reads

Effective long-term solution to therapeutic remission in Inflammatory Bowel Disease: Role of Azathioprine.

Biomed Pharmacother 2018 Apr 5;100:8-14. Epub 2018 Feb 5.

University of Pretoria, Faculty of Health Sciences, School of Medicine, Department of Physiology, South Africa. Electronic address:

Azathioprine (AZA) is a well-known immunosuppressant used for many years for its ability to ensure long term disease remission in inflammatory bowel diseases (IBD) at an affordable cost to the public. However, the side effect profile has raised many concerns with numerous investigations into the risk, cause and prevention of these effects. Much of the side effect profile of AZA can be linked to a single nucleotide polymorphism (SNP) in the thiopurine methyltransferase (TPMT) gene which ensures the breakdown and efficacy of AZA. Read More

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http://dx.doi.org/10.1016/j.biopha.2018.01.152DOI Listing
April 2018
2 Reads
2.020 Impact Factor

[Usefulness of thiopurine methyltransferase polymorphism study and metabolites measurement for patients treated by azathioprine].

Rev Med Interne 2018 Jun 19;39(6):421-426. Epub 2018 Jan 19.

Service de médecine interne, hôpital du Haut-Lévêque, avenue Magellan, 33604 Pessac, France.

Azathioprine is widely used in internal medicine and frequently implicated in occurrence of adverse events. Among these adverse events the bone marrow suppression, a dose-related one, is the most serious because of is potential morbidity and mortality. Severe myelosuppression, associated with abnormal AZA metabolism, is linked to the thiopurine methyltransferase (TPMT) genetic polymorphism that results in a high variability of its activity with 89% of patients with a normal activity, 11% with an intermediate activity, and 0. Read More

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http://dx.doi.org/10.1016/j.revmed.2017.12.007DOI Listing
June 2018
6 Reads

ITPA Activity in Children Treated by Azathioprine: Relationship to the Occurrence of Adverse Drug Reactions and Inflammatory Response.

Basic Clin Pharmacol Toxicol 2018 Jun 26;122(6):588-595. Epub 2018 Feb 26.

UMR CNRS 5305, Clinical Pharmacy, Pharmacokinetics and Drug Evaluation, Université de Lyon, Université Lyon 1, Lyon, France.

Azathioprine (AZA), a thiopurine drug, is widely used in the treatment of children with immunological diseases such as inflammatory bowel disease (IBD) and autoimmune hepatitis (AIH); however, interindividual variability in the occurrence of adverse drug reactions (ADRs) and drug response is observed. This study investigated (i) the relationships between inosine triphosphate pyrophosphatase (ITPA) activity, an enzyme involved in thiopurine metabolism, and the occurrence of ADRs in children with immunological disease on AZA therapy, and (ii) the relationship between ITPA activity and the inflammatory activity observed in children with IBD. ITPA and TPMT activities were determined in 106 children with immunological disease on AZA therapy. Read More

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http://dx.doi.org/10.1111/bcpt.12958DOI Listing
June 2018
12 Reads

Allopurinol in combination with thiopurine induces mucosal healing and improves clinical and metabolic outcomes in IBD.

Therap Adv Gastroenterol 2017 Nov 11;10(11):819-827. Epub 2017 Oct 11.

McGill Center for IBD, Research Institute of McGill University Health Center, MGH Campus, C10.145, 1650 Cedar Avenue, Montreal, Quebec, H3G 1A4, Canada.

Background: Thiopurines, azathioprine (AZA) and 6-mercaptopurine (6-MP) are common maintenance medications for inflammatory bowel disease (IBD). Excessive methylation thiopurine methyltransferase (TPMT) frequently causes therapeutic failure. Allopurinol reduces excessive 6-methyl-mercaptopurine (6-MMP) while enhancing 6-thioguanine (6-TGN) levels. Read More

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http://dx.doi.org/10.1177/1756283X17733657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5673019PMC
November 2017
41 Reads

Thiopurine S-Methyltransferase Polymorphisms in Korean Dermatologic Patients.

Ann Dermatol 2017 Oct 25;29(5):529-535. Epub 2017 Aug 25.

Department of Dermatology, Severance Hospital, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea.

Background: Thiopurine S-methyltransferase (TPMT) is an important enzyme in the metabolism of thiopurines including azathioprine (AZA), 6-mercaptopurine, and 6-thioguanine. TPMT genotyping is widely used for screening of AZA-related toxicity during routine clinical practice in Korea. However, the data of TPMT genotypes and its AZA-related toxicity have not been studied in the field of dermatology. Read More

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http://dx.doi.org/10.5021/ad.2017.29.5.529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5597644PMC
October 2017
16 Reads

Biomarkers of adverse drug reactions.

Exp Biol Med (Maywood) 2018 02 26;243(3):291-299. Epub 2017 Sep 26.

1 Department of Molecular and Clinical Pharmacology, Wolfson Centre for Personalised Medicine, Institute of Translational Medicine, 4591 University of Liverpool , Liverpool L69 3GL, UK.

Adverse drug reactions can be caused by a wide range of therapeutics. Adverse drug reactions affect many bodily organ systems and vary widely in severity. Milder adverse drug reactions often resolve quickly following withdrawal of the casual drug or sometimes after dose reduction. Read More

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http://dx.doi.org/10.1177/1535370217733425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5813863PMC
February 2018
27 Reads

Thiopurine metabolite levels in patients with atopic dermatitis and/or chronic hand/foot eczema treated with azathioprine.

J Dermatolog Treat 2018 Jun 26;29(4):375-382. Epub 2017 Sep 26.

a Department of Dermatology , University Medical Center Utrecht , Utrecht , The Netherlands.

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. Read More

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http://dx.doi.org/10.1080/09546634.2017.1373738DOI Listing
June 2018
9 Reads

Point-Counterpoint: TPMT Genotyping for Azathioprine in Adult Medicine.

S D Med 2017 Apr;70(4):151-152

Department of Internal Medicine, Division of Rheumatology, University of South Dakota Sanford School of Medicine.

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April 2017
31 Reads

Relationship between Azathioprine metabolites and therapeutic efficacy in Chinese patients with neuromyelitis optica spectrum disorders.

BMC Neurol 2017 Jul 5;17(1):130. Epub 2017 Jul 5.

Neuroinfection and Neuroimmunology Center, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, 6 TiantanXili, Dongcheng District, Beijing, 100050, People's Republic of China.

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. Read More

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http://dx.doi.org/10.1186/s12883-017-0903-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5498874PMC
July 2017
24 Reads

ITPA Activity in Adults and Children Treated With or Without Azathioprine: Relationship Between TPMT Activity, Thiopurine Metabolites, and Co-medications.

Ther Drug Monit 2017 10;39(5):483-491

*Université de Lyon, Université Lyon 1, UMR CNRS 5305, Pharmacie Clinique, Pharmacocinétique et Evaluation du Médicament; †Hospices Civils de Lyon, Groupement Hospitalier Edouard Herriot, Laboratoire de Biologie Médicale Multi Sites du CHU de Lyon, unité de Pharmacocinétique Clinique; ‡Hospices Civils de Lyon, Groupement Hospitalier Edouard Herriot, Laboratoire de Biologie Médicale Multi Sites du CHU de Lyon, unité de Pharmacologie, Toxicologie et Eléments trace; and §Laboratoire des Pathogènes Emergents-Fondation Mérieux, Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, CNRS UMR5308, ENS de Lyon, UCBL1, Lyon, France.

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.

Methods: ITPA activity was determined in 183 adults and 138 children with or without AZA therapy. Read More

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http://dx.doi.org/10.1097/FTD.0000000000000430DOI Listing
October 2017
20 Reads

Thiopurine S-Methyltransferase as a Pharmacogenetic Biomarker: Significance of Testing and Review of Major Methods.

Cardiovasc Hematol Agents Med Chem 2017 Nov;15(1):23-30

Department of Hematopoietic Pathologies, Institute of Hematology and Blood Transfusion, Baku, Azerbaijan.

Background: Thiopurine S-methyltransferase (TPMT) enzyme metabolizes thiopurine drugs which are widely used in various disciplines as well as in leukemias. Individual enzyme activity varies depending on the genetic polymorphisms of TPMT gene located at chromosome 6. Up to 14% of population is known to have a decreased enzyme activity, and if treated with standard doses of thiopurines, these individuals are at a high risk of severe Adverse Drug Reactions (ADR) as myelosuppression, gastrointestinal intolerance, pancreatitis and hypersensitivity. Read More

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http://dx.doi.org/10.2174/1871525715666170529091921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5740490PMC
November 2017
45 Reads

Thiopurine S-methyltransferase polymorphisms in acute lymphoblastic leukemia, inflammatory bowel disease and autoimmune disorders: influence on treatment response.

Pharmgenomics Pers Med 2017 5;10:143-156. Epub 2017 May 5.

Departments of Pediatrics and Pharmacology, CHU Sainte-Justine Research Center, University of Montreal, Montreal, QC, Canada.

The () gene encodes for the TPMT enzyme that plays a crucial role in the metabolism of thiopurine drugs. Genetic polymorphisms in this gene can affect the activity of the TPMT enzyme and have been correlated with variability in response to treatment with thiopurines. Advances in the pharmacogenetics of allowed the development of dosing recommendations and treatment strategies to optimize and individualize prescribing thiopurine in an attempt to enhance treatment efficacy while minimizing toxicity. Read More

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http://dx.doi.org/10.2147/PGPM.S108123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5428801PMC
May 2017
22 Reads

Role of Allopurinol in Optimizing Thiopurine Therapy in Patients with Autoimmune Hepatitis: A Review.

J Clin Exp Hepatol 2017 Mar 6;7(1):55-62. Epub 2017 Feb 6.

Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India.

Autoimmune hepatitis (AIH) is a chronic immune mediated liver disease characterized by elevated transaminases, hyper gammaglobulinemia, presence of autoantibodies and interface hepatitis in the absence of a known etiology of liver disease. Thiopurines (azathioprine [AZA]/6-mercaptopurine [6MP]) and steroids remain the first line of treatment of AIH in both children and adults. However, a small proportion of AIH patients are either non-responders or develop side effects with AZA. Read More

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http://dx.doi.org/10.1016/j.jceh.2017.01.115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5357743PMC
March 2017
12 Reads
2 Citations

Azathioprine Therapy in a Pediatric TPMT-Deficient Patient-Still an Option.

Ther Drug Monit 2017 02;39(1):1-4

*Department of Clinical Pharmacy and Toxicology, Zuyderland Medical Centre, Sittard-Geleen;†Department of Pediatrics, Zuyderland Medical Centre, Heerlen; and‡Department of Clinical Pharmacy and Toxicology, Zuyderland Medical Centre, Heerlen, the Netherlands.

We describe the case of a pediatric patient on azathioprine therapy with previously undiagnosed homozygote thiopurine S-methyltransferase (TPMT) deficiency, resulting in myelotoxic thiopurine metabolite levels. The patient was successfully treated with a very low azathioprine dose of 50 mg once a week (4% of standard dose), guided by frequent thiopurine metabolite measurement and a close clinical surveillance. We demonstrate that azathioprine therapy still might be an effective and safe therapeutic option in pediatric thiopurine S-methyltransferase-deficient IBD patients. Read More

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http://dx.doi.org/10.1097/FTD.0000000000000366DOI Listing
February 2017
8 Reads

LC-MS/MS Analysis of Erythrocyte Thiopurine Nucleotides and Their Association With Genetic Variants in Patients With Neuromyelitis Optica Spectrum Disorders Taking Azathioprine.

Ther Drug Monit 2017 02;39(1):5-12

*Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University; †Department of Clinical Pharmacology, College of Pharmaceutical Sciences, Capital Medical University; and ‡Neuroinfection and Neuroimmunology Center, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Background: Azathioprine is a first-line drug in treating neuromyelitis optica spectrum disorders (NMOSD). To exhibit its bioactivity, azathioprine needs to be converted to thiopurine nucleotides (TPNs) including 6-thioguanine nucleotides (6-TGNs) and 6-methylmercaptopurine nucleotides (6-MMPNs) that are affected by genetic polymorphisms. This study aims to develop an LC-MS/MS method for the analysis of erythrocyte concentrations of TPNs and to evaluate their associations with variants of various genes (MTHFR, TPMT, HLA, SLC29A1, SLC28A2, SLC28A3, ABCB1, and ABCC4) in patients with NMOSD. Read More

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http://dx.doi.org/10.1097/FTD.0000000000000362DOI Listing
February 2017
20 Reads

Genes implicated in thiopurine-induced toxicity: Comparing TPMT enzyme activity with clinical phenotype and exome data in a paediatric IBD cohort.

Sci Rep 2016 10 5;6:34658. Epub 2016 Oct 5.

Human Genetics and Genomic medicine, University of Southampton, Southampton, UK.

The aim of our study was to assess the utility of next generation sequencing (NGS) for predicting toxicity and clinical response to thiopurine drugs in paediatric patients with inflammatory bowel disease. Exome data for 100 patients were assessed against biochemically measured TPMT enzyme activity, clinical response and adverse effects. The TPMT gene and a panel of 15 other genes implicated in thiopurine toxicity were analysed using a gene based statistical test (SKAT-O test). Read More

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http://dx.doi.org/10.1038/srep34658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5050412PMC
October 2016
21 Reads

Measuring Erythrocyte Thiopurine Methyltransferase Activity in Children-Is It Helpful?

J Pediatr 2016 12 15;179:216-218. Epub 2016 Sep 15.

Department of Pediatric Nephrology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom.

Objective: To assess the profile of thiopurine transmethyltransferase (TPMT) enzyme activities in children and discuss the utility of measuring TPMT levels before commencing azathioprine therapy.

Study Design: Retrospective study in a single pediatric center of all patients who had TPMT enzyme assay measured during a 3-year period before the start of azathioprine therapy. Patients' TPMT enzyme activities were classified as normal (26-50 pmol/h/mgHb), intermediate (10-25 pmol/h/mgHb), and deficient (<10 pmol/h/mgHb). Read More

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http://dx.doi.org/10.1016/j.jpeds.2016.08.073DOI Listing
December 2016
22 Reads

Thiopurines in the Management of Crohn's Disease: Safety and Efficacy Profile in Patients with Normal TPMT Activity-A Retrospective Study.

Can J Gastroenterol Hepatol 2016 29;2016:1034834. Epub 2016 Mar 29.

Division of Gastroenterology, McGill University Health Center, 1650 Cedar Avenue, C7-200, Montreal, QC, Canada H3G 1A4.

Background and Aims. Thiopurines are used in the treatment of Crohn's disease (CD) and thiopurine S-methyltransferase (TPMT) activity can guide thiopurine dosing to avoid adverse events. This retrospective study evaluated the safety and efficacy of starting thiopurines at low dose versus full dose in patients with CD and normal TPMT. Read More

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http://dx.doi.org/10.1155/2016/1034834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4904638PMC
March 2017
31 Reads

Nucleoside diphosphate-linked moiety X-type motif 15 C415T variant as a predictor for thiopurine-induced toxicity in Indian patients.

J Gastroenterol Hepatol 2017 Mar;32(3):620-624

Department of Biochemistry, P. D. Hinduja National Hospital and Medical Research Centre, Mumbai, India.

Background And Aim: Interindividual variation seen in the thiopurine metabolism is attributed to the genetic variant in thiopurine methyltransferase (TPMT) gene leading to myelosuppression. In Asians, the thiopurine-induced toxicity is not completely explained by TPMT variants. Literature indicates that a newer genetic variant in nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15) gene is associated with thiopurine intolerance. Read More

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http://dx.doi.org/10.1111/jgh.13494DOI Listing
March 2017
34 Reads

Further evidence that a variant of the gene NUDT15 may be an important predictor of azathioprine-induced toxicity in Chinese subjects: a case report.

J Clin Pharm Ther 2016 Oct 6;41(5):572-4. Epub 2016 Jul 6.

Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

What Is Known And Objective: Thiopurine methyltransferase (TPMT) enzyme is an important component in the metabolism of azathioprine (AZA). Its mutation may lead to AZA-induced toxicity. The dysfunctional genetic variant TPMT *3C is of low frequency among Asians. Read More

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http://dx.doi.org/10.1111/jcpt.12420DOI Listing
October 2016
15 Reads

A Simple Method for TPMT and ITPA Genotyping Using Multiplex HRMA for Patients Treated with Thiopurine Drugs.

Mol Diagn Ther 2016 10;20(5):493-9

Institute of Human Genetics, Polish Academy of Sciences, ul. Strzeszynska 32, 60-479, Poznan, Poland.

Thiopurine methyltransferase (TPMT) and inosine triphosphatase (ITPA) are crucial enzymes involved in the metabolism of thiopurine drugs: azathioprine and 6-mercaptopurine, used in the treatment of leukemia or inflammatory bowel diseases (IBD). The activity in these enzymes correlates with the genetic polymorphism of the TPMT and ITPA genes, respectively, which determines an individual reaction and dosing of thiopurines. Three main TPMT alleles: TPMT*2 (c. Read More

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http://dx.doi.org/10.1007/s40291-016-0217-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5021755PMC
October 2016
37 Reads

Measurement of red blood cell 6-thioguanine nucleotide is beneficial in azathioprine maintenance therapy of Chinese Crohn's disease patients.

Scand J Gastroenterol 2016 Sep 6;51(9):1093-9. Epub 2016 May 6.

a Department of Gastroenterology , The First Affiliated Hospital of Anhui Medical University , Hefei , Anhui , People's Republic of China ;

Objective: It remains controversial whether 6-thioguanine nucleotide (6-TGN)-based dose adjusting can be beneficial in azathioprine (AZA) therapy. This study is designed to assess the role of 6-TGN concentrations in maintaining clinical remission in Chinese patients with Crohn's disease (CD).

Material And Method: We performed a prospective observational study and collected data of CD patients in the First Affiliated Hospital of Anhui Medical University from June 2013 to April 2014. Read More

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http://dx.doi.org/10.3109/00365521.2016.1161068DOI Listing
September 2016
31 Reads

Prospective Evaluation of Pharmacogenomics and Metabolite Measurements upon Azathioprine Therapy in Inflammatory Bowel Disease: An Observational Study.

Medicine (Baltimore) 2016 Apr;95(15):e3326

From the Department of Gastroenterology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou (ZF, CP, CY, XF); Department of Gastroenterology, the First Affiliated Hospital, Sun Yat-sen University (ZF, GX, CB, XY, CM, HP); Department of Gastroenterology, the Sixth Affiliated Hospital of Sun Yat-sen University (GX, HP); Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University (DL, LH, WX, BH, ZL, HM); and Department of Pharmacology, the First Affiliated Hospital of Jinan University (LH), Guangzhou, China).

Up to approximately 40% to 50% of patients discontinue thiopurine therapy during the course of inflammatory bowel disease (IBD). We investigated the role of the metabolite thiopurine in IBD treatment. This was a prospective study. Read More

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http://dx.doi.org/10.1097/MD.0000000000003326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4839824PMC
April 2016
23 Reads

Genetic Predictors of Azathioprine Toxicity and Clinical Response in Patients with Inflammatory Bowel Disease.

J Popul Ther Clin Pharmacol 2016 22;23(1):e26-36. Epub 2016 Feb 22.

Background: Thiopurines (Azathioprine (AZA) and 6-Mercaptopurine (6-MP) are considered a well-established therapy for patients with Inflammatory Bowel Disease (IBD) including ulcerative colitis (UC) and Crohn's Disease (CD). However, nearly 20% of patients discontinue thiopurines due to adverse events. Functional polymorphisms of several enzymes involved in the metabolism of thiopurines have been linked with toxicity. Read More

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January 2017
19 Reads

TPMT and ITPA genetic variants in Lithuanian inflammatory bowel disease patients: Prevalence and azathioprine-related side effects.

Adv Med Sci 2016 Mar 10;61(1):135-40. Epub 2015 Dec 10.

Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania; Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania. Electronic address:

Purpose: Inter-individual thiopurine metabolism variability can influence treatment outcomes in inflammatory bowel disease (IBD) patients. Genetic polymorphisms in thiopurine methyltransferase (TPMT) and inosine triphosphate pyrophosphatase (ITPA) were linked with toxicity of azathioprine (AZA). The aim of the study was to investigate frequencies of TPMT and ITPA polymorphisms in Lithuanian IBD patients and analyze their association with AZA-related adverse events. Read More

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http://dx.doi.org/10.1016/j.advms.2015.09.008DOI Listing
March 2016
31 Reads

Association between Thiopurine S-Methyltransferase Polymorphisms and Azathioprine-Induced Adverse Drug Reactions in Patients with Autoimmune Diseases: A Meta-Analysis.

PLoS One 2015 3;10(12):e0144234. Epub 2015 Dec 3.

Department of Laboratory Medicine, Southwest Hospital, Third Military Medical University, Chongqing, China.

Purpose: Azathioprine (AZA) is widely used as an immunosuppressive drug in autoimmune diseases, but its use is limited by significant adverse drug reactions (ADRs). Thiopurine S-methyltransferase (TPMT) is an important enzyme involved in AZA metabolism. Several clinical guidelines recommend determining TPMT genotype or phenotype before initiating AZA therapy. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0144234PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4669175PMC
June 2016
17 Reads

The impact of glutathione S-transferase genotype and phenotype on the adverse drug reactions to azathioprine in patients with inflammatory bowel diseases.

J Pharmacol Sci 2015 Oct 6;129(2):95-100. Epub 2015 Mar 6.

Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, PR China. Electronic address:

Azathioprine (AZA) is a thiopurine prodrug which is widely used in patients with inflammatory bowel disease (IBD). However, the use is limited in one-third of patients because of adverse drug reactions (ADRs) or a lack of clinical response. It has been considered that the polymorphic enzyme thiopurine S-methyltransferase (TPMT) plays an important role in the in vivo process of AZA and the occurrence of its myelotoxicity. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S13478613150005
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http://dx.doi.org/10.1016/j.jphs.2015.02.013DOI Listing
October 2015
12 Reads

A Prospective Study Evaluating Metabolic Capacity of Thiopurine and Associated Adverse Reactions in Japanese Patients with Inflammatory Bowel Disease (IBD).

PLoS One 2015 11;10(9):e0137798. Epub 2015 Sep 11.

Department of Internal Medicine, Division of Gastroenterology and Hepatology, The Jikei University School of Medicine (Kashiwa Hospital), Chiba, Japan.

Azathioprine (AZA) is frequently used in patients with inflammatory bowel disease (IBD). However, toxic adverse reactions frequently develop and limit the clinical benefits. Currently, the precise mechanisms underlying thiopurine-related toxicity are not well understood. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0137798PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4567281PMC
May 2016
23 Reads

Impact of Genetic Polymorphisms on 6-Thioguanine Nucleotide Levels and Toxicity in Pediatric Patients with IBD Treated with Azathioprine.

Inflamm Bowel Dis 2015 Dec;21(12):2897-908

Departments of *Laboratory Medicine and Genetics and †Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; ‡Department of Pediatrics, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea; and §Biostatistics Team, Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background: Thiopurine-related toxicity results in discontinuation of therapy in up to 30% of patients with inflammatory bowel disease. Although thiopurine S-methyltransferase (TPMT) is implicated in toxicity, not all toxicity can be attributed to TPMT polymorphisms. We investigated the effects of polymorphisms of genes involved in thiopurine and folate metabolism pathways on 6-thioguanine nucleotide levels and toxicity. Read More

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http://pdfs.journals.lww.com/ibdjournal/2015/12000/Impact_of
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http://content.wkhealth.com/linkback/openurl?sid=WKPTLP:land
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http://dx.doi.org/10.1097/MIB.0000000000000570DOI Listing
December 2015
23 Reads
6 Citations
4.464 Impact Factor

TPMT Polymorphism: When Shield Becomes Weakness.

Interdiscip Sci 2016 Jun 22;8(2):150-5. Epub 2015 Aug 22.

Bioinformatics Division, Department of Bioscience and Biotechnology, Banasthali University, Tonk, India.

Thiopurine methyltransferase (TPMT) is a cytoplasmic transmethylase present in both prokaryotes and eukaryotes. In humans, it shows its presence in almost all of the tissues, predominantly in liver and kidney. TPMT is one of the important metabolic enzymes of phase II metabolic pathway and catalyzes methylation of thiopurine drugs such as azathioprine, 6-thioguanine and 6-mercaptopurine, which are used to treat patients with neoplasia and autoimmune disease as well as transplant recipients. Read More

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http://link.springer.com/10.1007/s12539-015-0111-1
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http://dx.doi.org/10.1007/s12539-015-0111-1DOI Listing
June 2016
19 Reads

Identification of Patients With Variants in TPMT and Dose Reduction Reduces Hematologic Events During Thiopurine Treatment of Inflammatory Bowel Disease.

Gastroenterology 2015 Oct 11;149(4):907-17.e7. Epub 2015 Jun 11.

Department of Human Genetics, Donders Centre for Neuroscience, Radboud university medical center, Nijmegen, The Netherlands; Department of Psychiatry, Donders Centre for Neuroscience, Radboud university medical center, Nijmegen, The Netherlands.

Background & Aims: More than 20% of patients with inflammatory bowel disease (IBD) discontinue thiopurine therapy because of severe adverse drug reactions (ADRs); leukopenia is one of the most serious ADRs. Variants in the gene encoding thiopurine S-methyltransferase (TPMT) alter its enzymatic activity, resulting in higher levels of thiopurine metabolites, which can cause leukopenia. We performed a prospective study to determine whether genotype analysis of TPMT before thiopurine treatment, and dose selection based on the results, affects the outcomes of patients with IBD. Read More

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http://dx.doi.org/10.1053/j.gastro.2015.06.002DOI Listing
October 2015
54 Reads

Update on thiopurine pharmacogenetics in inflammatory bowel disease.

Pharmacogenomics 2015 Jul 12;16(8):891-903. Epub 2015 Jun 12.

Department of Medicine, University of Otago Christchurch, PO Box 4345, Christchurch, New Zealand.

Azathioprine and 6-mercaptopurine remain pivotal therapies for the maintenance of disease remission in patients with Crohn's disease and ulcerative colitis. While thiopurine S-methyltransferase deficiency was the first pharmacogenetic phenomenon to be recognized to influence thiopurine toxicity and reliably predict leukopenia, it does not predict other adverse effects, nor does it explain most cases of thiopurine resistance. In recent years, a number of other genetic polymorphisms have received increasing attention in the literature. Read More

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http://dx.doi.org/10.2217/pgs.15.29DOI Listing
July 2015
11 Reads

Body Mass Index and Smoking Affect Thioguanine Nucleotide Levels in Inflammatory Bowel Disease.

J Crohns Colitis 2015 Aug 12;9(8):640-6. Epub 2015 May 12.

Department of Gastroenterology, Royal Liverpool University Hospital, Liverpool, UK

Introduction: Optimal levels of the thiopurine metabolite, 6-thioguanine nucleotides [6-TGN] correlate with remission of inflammatory bowel disease [IBD]. Apart from variations in the thiopurine methyl transferase [TPMT] gene, little is known about other predictors of 6-TGN levels. Obesity adversely affects response to infliximab and adalimumab and clinical course in IBD, but little is known about the interaction of thiopurines and obesity. Read More

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http://dx.doi.org/10.1093/ecco-jcc/jjv084DOI Listing
August 2015
11 Reads

Plasma thiopurine S-methyltransferase levels and azathioprine-related adverse events in patients with Behçet's disease.

Clin Exp Rheumatol 2015 Nov-Dec;33(6 Suppl 94):S40-5. Epub 2015 May 1.

Department of Internal Medicine, Division of Rheumatology, Ege University School of Medicine, Izmir, Turkey.

Objectives: Thiopurine S-methyltransferase (TPMT) is the key enzyme inactivating azathioprine (AZA), an immunosuppressive agent commonly used for treating inflammatory diseases including Behçet's disease (BD), systemic lupus erythematosus (SLE) and systemic vasculitis. Low TPMT levels facilitate occurrence of AZA-related adverse effects. We investigated TPMT levels in patients with BD, compared to healthy controls and patients with SLE or systemic vasculitis. Read More

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January 2016
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Relationship between azathioprine dosage, 6-thioguanine nucleotide levels, and therapeutic response in pediatric patients with IBD treated with azathioprine.

Inflamm Bowel Dis 2015 May;21(5):1054-62

Departments of *Laboratory Medicine and Genetics, and †Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; ‡Department of Pediatrics, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea; and §Biostatistics Team, Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background: Azathioprine (AZA) is commonly used to treat IBD either alone or in combination with mesalazine. However, there are relatively few studies concerning the relationship between AZA dose, thiopurine metabolite levels, and therapeutic response in pediatric patients treated with both AZA and mesalazine.

Methods: We retrospectively investigated the relationship between AZA dose, thiopurine metabolite levels, and therapeutic response in 137 pediatric patients with IBD treated with AZA using multilevel analysis. Read More

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http://dx.doi.org/10.1097/MIB.0000000000000347DOI Listing
May 2015
14 Reads
6 Citations
4.464 Impact Factor

Thiopurine metabolites variations during co-treatment with aminosalicylates for inflammatory bowel disease: effect of N-acetyl transferase polymorphisms.

World J Gastroenterol 2015 Mar;21(12):3571-8

Gabriele Stocco, Giuliana Decorti, Department of Life Sciences, University of Trieste, I-34127 Trieste, Italy.

Aim: To evaluate variation of the concentration of thiopurine metabolites after 5-aminosalicylate (5-ASA) interruption and the role of genetic polymorphisms of N-acetyl transferase (NAT) 1 and 2.

Methods: Concentrations of thioguanine nucleotides (TGN) and methymercaptopurine nucleotides (MMPN), metabolites of thiopurines, were measured by high performance liquid chromatography in 12 young patients (3 females and 9 males, median age 16 years) with inflammatory bowel disease (6 Crohn's disease and 6 ulcerative colitis) treated with thiopurines (7 mercaptopurine and 5 azathioprine) and 5-ASA. Blood samples were collected one month before and one month after the interruption of 5-ASA. Read More

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http://dx.doi.org/10.3748/wjg.v21.i12.3571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4375579PMC
March 2015
12 Reads

Pharmacogenetics of inflammatory bowel disease.

Pharmacogenomics 2014 Dec;15(16):2049-62

Division of Gastroenterology, Medical School, University of Ioannina, Greece.

Pharmacogenetic studies have been performed for almost all classes of drugs that have been used in IBD but very few have generated consistent findings or have been replicated. The genetic test that has been approved for clinical practice is TPMT testing prior to starting treatment with thiopurine drugs. Research in IBD pharmacogenetics has focused on prediction of drug efficacy and toxicity by identifying polymorphisms in the genes encoding enzymes that are involved in metabolic pathways. Read More

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http://dx.doi.org/10.2217/pgs.14.154DOI Listing
December 2014
7 Reads