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UTILIDAD DE LA DETERMINACION DE LA ACTIVIDAD DE LA TIOPURINA METILTRANSFERASA PARA EL AJUSTE DE LA DOSIS DE AZATIOPRINA O MERCAPTOPURINA
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UTILIDAD DE LA DETERMINACION DE LA ACTIVIDAD DE LA TIOPURINA METILTRANSFERASA PARA EL AJUSTE DE LA DOSIS DE AZATIOPRINA O MERCAPTOPURINA

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La determinación de la actividad de la TPMT constituye una atractiva opción para individualizar la dosis de AZA o MP y prevenir el riesgo de efectos adversos.
Autor:
Javier P. Gisbert
Columnista Experto de SIIC

Institución:
Universidad Autónoma de Madrid (UAM)


Artículos publicados por Javier P. Gisbert
Recepción del artículo
22 de Febrero, 2010
Aprobación
15 de Septiembre, 2010
Primera edición
10 de Noviembre, 2010
Segunda edición, ampliada y corregida
7 de Junio, 2021

Resumen
La monitorización de la actividad de la tiopurina metiltransferasa (TPMT) se emplea para identificar a los pacientes tratados con azatioprina (AZA) y mercaptopurina (MP) que presentan mayor riesgo de mielotoxicidad. La actividad de la TPMT en la población general sigue una distribución trimodal, en la que aproximadamente el 11% de los individuos son heterocigotos y el 0.3% homocigotos para el alelo de baja actividad. Existen dos estrategias para identificar los pacientes con deficiencia de TPMT: la medición del fenotipo y del genotipo, con una elevada concordancia entre ambas técnicas. Se demostró una notable correlación entre el fenotipo o el genotipo de baja actividad de la TPMT y el riesgo de mielotoxicidad. Los pacientes con un genotipo homocigoto de alta actividad (o con actividad normal de la TPMT) deberían recibir dosis de inmunosupresores que hayan demostrado ser claramente eficaces. En aquellos enfermos con genotipo o fenotipo homocigoto de baja actividad de la TPMT se debería contraindicar el empleo de AZA/MP o, en todo caso, sería obligado administrar dosis muy reducidas de estos fármacos. En resumen, la determinación de la actividad de la TPMT constituye una atractiva opción para individualizar la dosis de AZA o MP y prevenir el riesgo de efectos adversos, aunque está por demostrarse si esta estrategia debe aplicarse rutinariamente en todos los pacientes. En cualquier caso, el fenotipo o el genotipo asociado con el déficit de TPMP explica únicamente un porcentaje de casos de mielotoxicidad, por lo que los controles analíticos periódicos deben seguir realizándose en estos pacientes a pesar de que la función de esta enzima sea normal.

Palabras clave
enfermedad de Crohn, colitis ulcerosa, enfermedad inflamatoria intestinal, azatioprina, mercaptopurina, tiopurina metiltransferasa, TPMT


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Abstract
Thiopurine methyltransferase (TPMT) activity monitoring has been used to identify those patients treated with azathioprine and mercaptopurine having a higher risk of myelotoxicity. A trimodal distribution of inheritance of TPMT activity has been described, with most of the patients (about 90%) being of the wild type, approximately 10% being heterozygous, and less than 0.5% being homozygous deficient. Several studies have demonstrated a high concordance between genotype and phenotype classification of TPMT activity. A high correlation between the low TPMT activity genotype/phenotype classification and the risk of myelotoxicity has been reported. High activity homozygous patients (with normal TPMT activity) should receive an effective (high) dose; homozygous patients (with low TPMT activity) should not receive azathioprine, although sometimes a very low dose (10%-15% of standard dose) could be administered. In summary, TPMT activity monitoring may be considered an encouraging strategy to choose, in a more individualized and safer way, the thiopurine dose. However, TPMT deficiency phenotype or genotype explains a variable proportion of myelotoxicity cases, but in no way explains all episodes of bone marrow suppression. Therefore, systematic blood controls should be done in azathioprine-treated patients despite TPMT phenotype/genotype being normal.

Key words
Crohn's disease, ulcerative colitis, inflammatory bowel disease, azathioprine, mercaptopurine, thiopurine methyltransferase, TPMT


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Especialidades
Principal: Bioquímica, Farmacología
Relacionadas: Diagnóstico por Laboratorio, Gastroenterología, Genética Humana, Hematología, Inmunología, Medicina Farmacéutica, Medicina Interna, Oncología, Reumatología



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Bibliografía del artículo


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