343 results match your criteria Azathioprine Metabolism and TPMT


Reducing risk in thiopurine therapy.

Xenobiotica 2020 Jan 12;50(1):101-109. Epub 2019 Nov 12.

Purine Research Laboratory, Viapath, St Thomas' Hospital, London, UK.

The thiopurine drugs azathioprine and mercaptopurine are effective in the treatment of disorders of immune regulation and acute lymphoblastic leukaemia. Although developed in the 1950s, thiopurines remained relevant in the anti-tumour necrosis factor biologic era, finding widespread use as a co-immunomodulator. Step changes in the management of patients treated with thiopurines have reduced the incidence of severe, sometimes life-threatening toxicity. Read More

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http://dx.doi.org/10.1080/00498254.2019.1688424DOI Listing
January 2020
1 Read

Severe pancytopenia and aspergillosis caused by thioguanine in a thiopurine S-methyltransferase deficient patient: a case report.

Eur J Gastroenterol Hepatol 2019 12;31(12):1592-1596

Department of Clinical Pharmacy, St. Antonius Hospital, Nieuwegein.

Azathioprine and mercaptopurine are widely used in the treatment of inflammatory bowel disease. However, its use is limited by adverse drug event related to the relatively narrow therapeutic index of the active metabolites. Several patients discontinue treatment because of intolerable adverse events or toxicity such as leucopenia and hepatotoxicity. Read More

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http://dx.doi.org/10.1097/MEG.0000000000001504DOI Listing
December 2019

Genotype-based Treatment With Thiopurine Reduces Incidence of Myelosuppression in Patients With Inflammatory Bowel Diseases.

Clin Gastroenterol Hepatol 2019 Aug 22. Epub 2019 Aug 22.

Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address:

Background & Aims: Thiopurine-related myelosuppression (most frequently leukopenia) interferes with thiopurine therapy for patients with inflammatory bowel diseases (IBD). We investigated whether pretreatment analyses genetic variants associated with thiopurine-induced leukopenia could be used to effectively identify patients who required dose adjustments.

Methods: We performed a multicenter, prospective study of patients with IBD at 5 tertiary medical centers in Korea, from January 2016 through September 2018. Read More

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http://dx.doi.org/10.1016/j.cgh.2019.08.034DOI Listing
August 2019
3 Reads

Correlation between Thiopurine S-Methyltransferase Genotype and Adverse Events in Inflammatory Bowel Disease Patients.

Medicina (Kaunas) 2019 Aug 5;55(8). Epub 2019 Aug 5.

Department of General and Specialist Medicine, Gastroenterologia-U, Città della Salute e della Scienza di Torino, C.so Bramante 88, 10126 Turin, Italy.

In patients with inflammatory bowel diseases (IBD), the use of azathioprine results in adverse events at a rate of 5% to 20%. The aim of the study was to assess a possible correlation between genetic variability of the enzyme thiopurine S-methyltransferase (TPMT) and the development of toxicity to azathioprine. A retrospective, single center, blind, case-control study was conducted on 200 IBD patients, of whom 60 cases suspended azathioprine due to toxicity (leukopenia, pancreatitis, hepatitis, and nausea or vomiting), and 140 controls continued treatment with the drug without adverse events. Read More

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http://dx.doi.org/10.3390/medicina55080441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723288PMC
August 2019
3 Reads

Systematic review with meta-analysis: risk factors for thiopurine-induced leukopenia in IBD.

Aliment Pharmacol Ther 2019 09 25;50(5):484-506. Epub 2019 Jul 25.

Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology and Metabolism Research Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

Background: Thiopurine-induced leukopenia, a frequently observed and potentially life-threatening adverse event, complicates the clinical management of IBD patients.

Aim: To assess risk factors for thiopurine-induced leukopenia in IBD.

Methods: MEDLINE, EMBASE, BIOSIS and Cochrane library were searched for studies reporting at least one risk factor for thiopurine-induced leukopenia. Read More

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http://dx.doi.org/10.1111/apt.15403DOI Listing
September 2019
3 Reads

Thiopurine Therapy in Patients With Inflammatory Bowel Disease: A Focus on Metabolism and Pharmacogenetics.

Dig Dis Sci 2019 09 9;64(9):2395-2403. Epub 2019 Jul 9.

Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.

Thiopurines have been widely used for the maintenance of remission or steroid sparing in patients with inflammatory bowel disease. However, potential drug-related adverse events frequently interfere with their use. Indeed, drug withdrawals associated with adverse reactions have been reported in approximately 25% of patients. Read More

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http://dx.doi.org/10.1007/s10620-019-05720-5DOI Listing
September 2019

Azathioprine Biotransformation in Young Patients with Inflammatory Bowel Disease: Contribution of Glutathione-S Transferase M1 and A1 Variants.

Genes (Basel) 2019 04 4;10(4). Epub 2019 Apr 4.

Institute for Maternal and Child Health IRCCS Burlo Garofolo, 34137 Trieste, Italy.

The contribution of candidate genetic variants involved in azathioprine biotransformation on azathioprine efficacy and pharmacokinetics in 111 young patients with inflammatory bowel disease was evaluated. Azathioprine doses, metabolites thioguanine-nucleotides (TGN) and methylmercaptopurine-nucleotides (MMPN) and clinical effects were assessed after at least 3 months of therapy. Clinical efficacy was defined as disease activity score below 10. Read More

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http://dx.doi.org/10.3390/genes10040277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6523194PMC
April 2019
3 Reads

Modeling the Outcome of Systematic TPMT Genotyping or Phenotyping Before Azathioprine Prescription: A Cost-Effectiveness Analysis.

Mol Diagn Ther 2019 06;23(3):429-438

Service de Biochimie, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Université Paris Descates, 20, rue Leblanc, 75015, Paris, France.

Background: Thiopurine S-methyltransferase (TPMT) testing, either by genotyping or phenotyping, can reduce the incidence of adverse severe myelotoxicity episodes induced by azathioprine. The comparative cost-effectiveness of TPMT genotyping and phenotyping are not known.

Objective: Our aim was to assess the cost-effectiveness of phenotyping-based dosing of TPMT activity, genotyping-based screening and no screening (reference) for patients treated with azathioprine. Read More

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http://dx.doi.org/10.1007/s40291-019-00398-xDOI Listing
June 2019
4 Reads

Combined evaluation of genotype and phenotype of thiopurine S-methyltransferase (TPMT) in the clinical management of patients in chronic therapy with azathioprine.

Drug Metab Pers Ther 2019 03 6;34(1). Epub 2019 Mar 6.

Department of Laboratory Medicine, ASST Niguarda Hospital, Milan, Italy.

Background The thiopurine S-methyltransferase (TPMT)/azathioprine (AZA) gene-drug pair is one of the most well-known pharmacogenetic markers. Despite this, few studies investigated the implementation of TPMT testing and the combined evaluation of genotype and phenotype in multidisciplinary clinical settings where patients are undergoing chronic therapy with AZA. Methods A total of 356 AZA-treated patients for chronic autoimmune diseases were enrolled. Read More

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http://dx.doi.org/10.1515/dmpt-2018-0037DOI Listing
March 2019
29 Reads

[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
18 Reads

Do clinical and laboratory parameters predict thiopurine metabolism and clinical outcome in patients with inflammatory bowel diseases?

Eur J Clin Pharmacol 2019 Mar 4;75(3):335-342. Epub 2019 Jan 4.

Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, University of Zurich, Rämistrasse 100, CH-8091, Zürich, Switzerland.

Purpose: The thiopurines azathioprine and 6-mercaptopurine are frequently used for remission maintenance in patients with inflammatory bowel diseases. However, there are therapy failures, and it is unclear whether clinical and laboratory parameters can be used to predict thiopurine metabolite concentrations (as a surrogate for adequate remission maintenance therapy) and clinical outcome in these patients.

Methods: In this retrospective analysis of clinical routine patient data, multivariate statistical models based on Linear Mixed Models regression and Generalized Estimating Equations logistic regression were developed. Read More

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http://dx.doi.org/10.1007/s00228-018-02616-7DOI Listing
March 2019
8 Reads

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
10 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 2019 May 28;124(5):600-606. Epub 2018 Dec 28.

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
May 2019
29 Reads

Thiopurine Methyltransferase Genetic Polymorphisms and Activity and Metabolic Products of Azathioprine in Patients with Inflammatory Bowel Disease.

Endocr Metab Immune Disord Drug Targets 2019 ;19(4):541-547

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
January 2020
31 Reads

Clinical Pharmacogenetics Implementation Consortium Guideline for Thiopurine Dosing Based on TPMT and NUDT15 Genotypes: 2018 Update.

Clin Pharmacol Ther 2019 05 20;105(5):1095-1105. Epub 2019 Jan 20.

Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.

Thiopurine methyltransferase (TPMT) activity exhibits a monogenic codominant inheritance and catabolizes thiopurines. TPMT variant alleles are associated with low enzyme activity and pronounced pharmacologic effects of thiopurines. Loss-of-function alleles in the NUDT15 gene are common in Asians and Hispanics and reduce the degradation of active thiopurine nucleotide metabolites, also predisposing to myelosuppression. Read More

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http://doi.wiley.com/10.1002/cpt.1304
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http://dx.doi.org/10.1002/cpt.1304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6576267PMC
May 2019
34 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
48 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
17 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
12 Reads

Thiopurine-induced toxicity is associated with dysfunction variant of the human molybdenum cofactor sulfurase gene (xanthinuria type II).

Toxicol Appl Pharmacol 2018 08 20;353:102-108. Epub 2018 Jun 20.

Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University, General University Hospital in Prague, Prague, Czech Republic.

Background: The aim of our study was to identify the genetic background of thiopurine-induced toxicity in a patient with a wild-type thiopurine methyltransferase genotype and activity. A 38-year-old Caucasian woman presented with cutaneous necrotizing vasculitis pancytopenia one month after starting azathioprine therapy.

Methods: During a routine biochemical follow-up of the patient, undetectable serum uric acid (<10 μl) was observed. Read More

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http://dx.doi.org/10.1016/j.taap.2018.06.015DOI Listing
August 2018
9 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
47 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
28 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
8 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
11 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
36 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
10 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
8 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
14 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
17 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
55 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
27 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
64 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
16 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
55 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
37 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
32 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
86 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
30 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
25 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
15 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
50 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
49 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
45 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
59 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
40 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
35 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
64 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
60 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
45 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
37 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
53 Reads