| Autor: |
Ribeiro AC; Department of Pharmaceutical Sciences, Faculty of Pharmacy, Federal University of Juiz de Fora, Juiz de Fora 36036-900, Minas Gerais, Brazil., Gerheim PSAS; Department of Pharmacology, Federal University of Juiz de Fora, Juiz de Fora 36036-900, Minas Gerais, Brazil., Chebli JMF; Division of Gastroenterology, Department of Internal Medicine, Federal University of Juiz de Fora, Juiz de Fora 36036-900, Minas Gerais, Brazil., Nascimento JWL; Laboratory of Clinical and Experimental Pharmacology, Department of Pharmacology, Federal University of Juiz de Fora, Juiz de Fora 36036-900, Minas Gerais, Brazil., de Faria Pinto P; Department of Biochemistry, Institute of Biological Sciences, Federal University of Juiz de Fora, Juiz de Fora 36036-900, Minas Gerais, Brazil. |
| Abstrakt: |
This study focuses on the use of thiopurines for treating inflammatory bowel diseases (IBD). These drugs undergo enzymatic changes within the body, resulting in active and inactive metabolites that influence their therapeutic effects. The research examines the role of genetic polymorphisms in the enzyme thiopurine S-methyltransferase (TPMT) in predicting the therapeutic response and adverse effects of thiopurine treatment. The TPMT genotype variations impact the individual responses to thiopurines. Patients with reduced TPMT activity are more susceptible to adverse reactions (AEs), such leukopenia, hepatotoxicity, pancreatitis, and nausea, which are common adverse effects of thiopurine therapy. The therapeutic monitoring of the metabolites 6-thioguanine nucleotides (6-TGN) and 6-methyl mercaptopurine (6-MMP) is proposed to optimize treatment and minimize AEs. Patients with higher 6-TGN levels tend to have better clinical responses, while elevated 6-MMP levels are linked to hepatotoxicity. Genotyping for TPMT before or during treatment initiation is suggested to tailor dosing strategies and enhance treatment efficacy while reducing the risk of myelosuppression. In conclusion, this study highlights the importance of considering genetic variations and metabolite levels in optimizing thiopurine therapy for IBD patients, focusing on balance therapeutic efficacy with the prevention of adverse effects and contributing to personalized treatment and better patient outcomes. |
