[Monitoring of thiopurine methyltransferase and thiopurine metabolites to optimize azathioprine therapy in inflammatory bowel disease].
Determination of the activity of thiopurine methyltransferase (TPMT) and of thiopurine metabolites (6-thioguanine and 6-methylmercaptopurine nucleotides) could be useful for individualized monitoring of azathioprine (AZA) and 6-mercaptopurine (6-MP) doses. TPMT activity in the general population follows a trimodal distribution, in which approximately 0.3% of the population is homozygotic for the low-activity allele. A notable correlation has been observed between the low TPMP activity genotype or phenotype and the risk of myelotoxicity. Patients with a high TPMT activity genotype or homozygous phenotype should receive immunosuppressive doses that have clearly been demonstrated to be effective. In contrast, in patients with a low TPMT activity genotype or homozygous phenotype, the use of AZA/6-MP should be contraindicated or only very small doses should be administered. Importantly, TPMP deficiency explains only some cases of myelotoxicity and consequently periodic laboratory testing should be performed in patients receiving AZA/6-MP, even though TPMP function may be normal. Currently, the utility of routine thiopurine metabolite determinations in patients undergoing AZA/6-MP therapy has not been established and this practice should be limited to specific situations such as lack of response to thiopurine therapy or the occurrence of thiopurine-related adverse effects. Randomized trials comparing the routine strategy of AZA/6-MP dosing (based exclusively on the patient's weight) versus individualized monitoring (based on quantification of TPMP activity and/or thiopurine metabolites) are required before definitive conclusions on the most effective alternative can be drawn.
Gisbert
Javier P
JP
Servicio de Aparato Digestivo. Hospital Universitario de La Princesa. Universidad Autónoma. Madrid. España. gisbert@meditex.es
González-Lama
Yago
Y
Maté
José
J
D000963:Antimetabolites / Q000378:metabolism / Q000627:therapeutic use*; D001379:Azathioprine / Q000378:metabolism / Q000627:therapeutic use*; D016903:Drug Monitoring; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000378:metabolism / Q000627:therapeutic use*; D015122:Mercaptopurine / Q000378:metabolism / Q000627:therapeutic use*; D008778:Methylthioinosine / Q000378:metabolism; D008780:Methyltransferases / Q000378:metabolism*; D010641:Phenotype; D013866:Thioguanine / Q000378:metabolism
D000963:Antimetabolites; D007166:Immunosuppressive Agents; D008778:Methylthioinosine; D015122:Mercaptopurine; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D013866:Thioguanine; D001379:Azathioprine