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Early therapeutic drug monitoring helps to identify inflammatory bowel disease patients with a high risk to fail thiopurine treatment.
Br J Clin Pharmacol
December 2024
Department of Gastroenterology and Hepatology, Maastricht University Medical Center, Maastricht, Netherlands.
Aims: Conventional thiopurines (azathioprine and mercaptopurine) remain standard therapy to maintain steroid sparing remission in inflammatory bowel disease (IBD), but are regularly discontinued due to adverse drug reactions (ADRs). Measurement of the metabolites 6-thioguanine nucleotides (6-TGN), 6-methylmercaptopurine ribonucleotides (6-MMPR) and the 6-MMPR/6-TGN ratio, may predict the development of these ADRs. Our aim was to evaluate whether early thiopurine metabolite measurements were associated with clinical outcomes.
View Article and Find Full Text PDFPharmacogenomic Assessment of Genes Implicated in Thiopurine Metabolism and Toxicity in a UK Cohort of Pediatric Patients With Inflammatory Bowel Disease.
Inflamm Bowel Dis
July 2024
Human Genetics and Genomic Medicine, University of Southampton, Southampton, United Kingdom.
Article Synopsis
- Thiopurine drugs are commonly prescribed for treating inflammatory bowel disease in children, but they can cause adverse effects, leading to discontinuation in some patients.
- A study of 487 pediatric patients found that 11% experienced myelosuppression and other toxicities such as gastroenterological issues (11%) and hepatotoxicity (4.5%).
- The research indicated that while certain genetic variants in TPMT and NUDT15 were expected to contribute to thiopurine toxicity, significant associations for toxicity were actually found in the AOX1 and DHFR genes among patients who did not carry these variants.
Drug reactive metabolite-induced hepatotoxicity: a comprehensive review.
Toxicol Mech Methods
July 2024
Department of Pharmacology, SVKM's NMIMS School of Pharmacy and Technology Management, Shirpur, Maharashtra, India.
Nowadays, drug-induced liver toxicity (DILT) is one of the main contributing factors to severe liver disease. In the United States (US) alone, DILT is the cause of more than 50% of instances of acute liver failure. Prescription or over-the-counter drugs, xenobiotics, and herbal and nutritional supplements can cause DILT and could produce anomalies in hepatic function tests.
View Article and Find Full Text PDFAntiviral Potential of Azathioprine and Its Derivative 6- Mercaptopurine: A Narrative Literature Review.
Pharmaceuticals (Basel)
January 2024
Grupo de Investigación en Ciencias Animales-GRICA, Facultad de Medicina Veterinaria y Zootecnia, Universidad Cooperativa de Colombia, Bucaramanga 680002, Colombia.
The use of azathioprine (AZA) in human medicine dates back to research conducted in 1975 that led to the development of several drugs, including 6-mercaptopurine. In 1958, it was shown that 6-mercaptopurine decreased the production of antibodies against earlier administered antigens, raising the hypothesis of an immunomodulatory effect. AZA is a prodrug that belongs to the thiopurine group of drugs that behave as purine analogs.
View Article and Find Full Text PDFEffects of allopurinol on 6-mercaptopurine metabolism in unselected patients with pediatric acute lymphoblastic leukemia: a prospective phase II study.
Haematologica
September 2024
Children's Cancer Centre, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Pediatrics, Institute for Clinical Sciences, University of Gothenburg.
Allopurinol can be used in maintenance therapy (MT) for pediatric acute lymphoblastic leukemia (ALL) to mitigate hepatic toxicity in patients with skewed 6-mercaptopurine metabolism. Allopurinol increases the erythrocyte levels of thioguanine nucleotides (e-TGN), which is the proposed main mediator of the antileukemic effect and decreases methyl mercaptopurine (e-MeMP) levels, associated with hepatotoxicity. We investigated the effects of allopurinol in thiopurine methyltransferase (TPMT) wild-type patients without previous clinical signs of skewed 6-mercaptopurine metabolism.
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