Unlabelled: The use of azathioprine (and its metabolite mercaptopurine) is limited by toxicity, especially myelosuppression, which is related to activity of the enzyme thiopurine S-methyltransferase (TPMT). TPMT activity varies between individuals and is considered deficient in one in 300 cases.
Aims & Methods: We identified TPMT activity within an ethnically diverse population of patients attending an inner-city hospital phlebotomy service. A total of 1000 subjects were recruited and analyzed with respect to age, sex and ethnicity.
Results: Samples were analyzed from 456 Caucasians, 342 South Asians and 180 Afro-Caribbeans. Six subjects had deficient TPMT activity (0.6%: four women, two men; four Caucasians, one Afro-Caribbean, one South Asian). TPMT activity (nmol 6-methylthioguanine (6-MTG)/gHb/h) ranged 0-76 (median [interquartile range]: 33 [28-39]). Enzyme activity was lower in Afro-Caribbeans (30 [25-37.5]) than Caucasians (34 [29-40]) and South Asians (33 [29-38]), which was significant after adjustment for age and sex (p < 0.0001). Activity was lower in women (p = 0.022), especially South Asian females (n = 194; 32 [28-36]), compared with (35 [30-40]) in men (n = 148; p = 0.002).
Conclusions: A higher prevalence of TPMT deficiency was recorded than in previous studies. Afro-Caribbeans have lower activity than Caucasians and South Asians. TPMT enzyme activity was lower among females, especially in South Asians.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.2217/14622416.9.3.303 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Efficacy and safety of azathioprine in patients with Cronkhite-Canada syndrome: a case series from Peking Union Medical College Hospital.
BMC Pharmacol Toxicol
December 2024
Department of Gastroenterology, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, No.1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, China.
Background: Cronkhite-Canada syndrome (CCS) is a rare non-hereditary chronic inflammatory disease characteristic of gastrointestinal polyps and ectodermal abnormalities. Corticosteroid therapy is the mainstay medication for CCS. Few studies indicated immunosuppressants might be the choices for patients with steroid refractory, steroid dependent or intolerant.
View Article and Find Full Text PDFUtilization and associated factors of TPMT testing among Australian adults receiving thiopurines: A national retrospective data-linkage study.
Pharmacotherapy
November 2024
The University of Sydney School of Pharmacy, Camperdown, New South Wales, Australia.
Introduction: Thiopurine drugs are metabolized by thiopurine methyltransferase (TPMT) and low TPMT activity can result in severe adverse drug reactions. Therefore, TPMT testing is recommended for individuals receiving thiopurines to reduce the risk of toxicity.
Objectives: The objectives of this study were to assess the rate of TPMT testing among individuals receiving thiopurines and explore factors associated with undergoing TPMT testing in Australia.
Contemporary and prospective use of azathioprine (AZA) in viral, rheumatic, and dermatological disorders: a review of pharmacogenomic and nanotechnology applications.
Naunyn Schmiedebergs Arch Pharmacol
November 2024
Department of Pharmacy Practice, Dr. D.Y. Patil Institute of Pharmaceutical Sciences and Research Pimpri, Pune, Maharashtra, India.
Article Synopsis
- Azathioprine (AZA), commonly used for autoimmune disorders and organ transplants, shows potential for modern applications in viral, rheumatic, and skin diseases.
- Advances in pharmacogenomics and nanotechnology may enhance AZA's effectiveness while reducing side effects, particularly by utilizing the active metabolites 6-mercaptopurine and 6-thioguanine.
- The study suggests that personalized medicine approaches, including genetic testing and innovative drug delivery systems, can improve treatment outcomes for conditions like systemic lupus erythematosus and psoriasis.
Genetic profiling of in the Slovenian population.
Pharmacogenomics
November 2024
University of Ljubljana, Faculty of Pharmacy, Aškerčeva 7, Ljubljana, 1000, Slovenia.
Article Synopsis
- This text discusses the use of pharmacogenomics to tailor thiopurine therapy based on genetic variants, initially focusing on its success in Asian populations but now recognized in European populations as well.
- Researchers sequenced specific gene regions in Slovenian individuals to evaluate the pharmacogenetic role of variants related to thiopurine therapy for patients with acute lymphoblastic leukemia (ALL).
- The study found several genetic variants, including one with known clinical relevance, but most variants were not linked to the dosage of thiopurines in ALL patients, suggesting the need for deeper studies in larger groups.
A Review of the Regulatory Challenges of Personalized Medicine.
Cureus
August 2024
Pharmacy, SRM College of Pharmacy, SRM Institute of Science and Technology (SRMIST), Chennai, IND.
Personalized medicine integrates genomics with clinical and familial histories, revolutionizing healthcare by tailoring treatments to individual patient characteristics. At its core, pharmacogenomics enables the customization of medication prescriptions based on genetic profiles, enhancing drug efficacy and safety. This precision medicine approach addresses disease diagnosis, prevention, and treatment, offering targeted therapies for conditions like autoimmune disorders, rheumatoid arthritis, and neoplastic conditions.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!