6merkaptopuriini

6-merkaptopuriini, also known as 6-mercaptopurine (6-MP), is a thiopurine antimetabolite used as chemotherapy and an immunosuppressant. It is employed in the treatment of acute lymphoblastic leukemia (ALL) and, in adults and children, inflammatory bowel diseases such as Crohn's disease and ulcerative colitis, often as part of combination regimens or maintenance therapy. It may also be used off-label for other autoimmune conditions.

6-MP is a purine analogue that, after oral administration, is activated inside cells by hypoxanthine-guanine phosphoribosyltransferase (HGPRT) to thioinosinic acid (T-IMP) and further to thioguanine nucleotides (6-TGN). These metabolites inhibit de novo purine synthesis and disrupt nucleic acid function, reducing proliferation of rapidly dividing cells, particularly lymphocytes. Some metabolites can be incorporated into DNA and RNA, contributing to cytotoxic effects.

Metabolism occurs mainly via xanthine oxidase, which inactivates 6-MP, and through methylation by TPMT; genetic variants in TPMT and in NUDT15 influence the risk of bone marrow suppression. Patients with low TPMT or NUDT15 activity are at higher risk of severe myelosuppression, necessitating dose adjustments or alternative therapies. Allopurinol and other xanthine oxidase inhibitors markedly increase 6-MP levels and toxicity, requiring substantial dose reductions when co-administered.

Adverse effects include bone marrow suppression, hepatotoxicity, pancreatitis, nausea, and increased infection risk. Therapeutic drug monitoring may include white blood cell counts during initiation and, when available, measurement of thiopurine metabolites to guide dosing and assess toxicity.