Split-dose administration of thiopurine drugs: a novel and effective strategy for managing preferential 6-MMP metabolism

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dc.contributor.authorShih, D. Q.
dc.contributor.authorNguyen, M.
dc.contributor.authorZheng, L.
dc.contributor.authorIbanez, P.
dc.contributor.authorMei, L.
dc.contributor.authorKwan, L. Y.
dc.contributor.authorBradford, K.
dc.contributor.authorTing, C.
dc.contributor.authorTargan, S. R.
dc.contributor.authorVasiliauskas, E. A.
dc.date.accessioned2024-01-10T13:43:38Z
dc.date.available2024-01-10T13:43:38Z
dc.date.issued2012
dc.description.abstractBackground Mercaptopurine and azathioprine (AZA) are efficacious in treating IBD. 6-tioguanine (6-TGN) levels correlate with therapeutic efficacy, whereas high 6-methylmercaptopurine (6-MMP) levels are associated with hepatotoxicity and myelotoxicity. Some IBD patients exhibit dose-limiting preferential 6-MMP production, which may lead to undesired side effects and impact efficacy. Aim To review the outcomes of thiopurine split-dosing in patients with preferential 6-MMP metabolism. Methods A retrospective chart review of 179 IBD patients treated at the Cedars-Sinai IBD Center with AZA or mercaptopurine was performed. Preferential 6-MMP metabolisers with 6-MMP levels greater than 7000 pmol/8 x 108 erythrocytes who underwent split-dosing were identified and assessed for biochemical and clinical responses to these dose modifications. Results A total of 20 of 179 patients met the criteria for preferential 6-MMP metabolism and underwent thiopurine split-dosing. Dividing the total daily thiopurine dose led to a reduction in 6-MMP levels (11785 vs. 5324 pmol/8 x 108 erythrocytes; P < 0.0001) without negatively affecting clinical disease activity or 6-TGN levels (239 vs. 216 pmol/8 x 108 erythrocytes; P = N.S.) and led to resolution of 6-MMP associated side effects (elevated transaminases, leucopenia and flu-like symptoms) in all but two patients. After mean follow-up of 36 months, 12 patients remained in clinical remission on split-dose mercaptopurine. Five of the remaining eight patients escalated to anti-TNF therapy, two progressed to surgery, and one switched to tioguanine therapy. Conclusion Split-dose administration of mercaptopurine/AZA represents an alternative option in IBD patients with preferential 6-MMP metabolism who might otherwise require steroid exposure or escalation of therapy.
dc.description.funderCedars-Sinai Medical Center Inflammatory Bowel & Immunobiology Research Institute
dc.description.funderNIH
dc.description.funderNATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
dc.fechaingreso.objetodigital2024-05-07
dc.format.extent10 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1111/j.1365-2036.2012.05206.x
dc.identifier.issn0269-2813
dc.identifier.pubmedidMEDLINE:22784257
dc.identifier.urihttps://doi.org/10.1111/j.1365-2036.2012.05206.x
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/78706
dc.identifier.wosidWOS:000307164600005
dc.information.autorucMedicina;Ibañez P ;S/I;135641
dc.issue.numero5
dc.language.isoen
dc.nota.accesocontenido parcial
dc.pagina.final458
dc.pagina.inicio449
dc.publisherWILEY-BLACKWELL
dc.revistaALIMENTARY PHARMACOLOGY & THERAPEUTICS
dc.rightsacceso restringido
dc.subjectINFLAMMATORY-BOWEL-DISEASE
dc.subjectT-CELL LYMPHOMA
dc.subjectCROHNS-DISEASE
dc.subjectLONG-TERM
dc.subjectMETHYLTRANSFERASE ACTIVITY
dc.subject6-MERCAPTOPURINE THERAPY
dc.subjectAZATHIOPRINE THERAPY
dc.subjectALLOPURINOL
dc.subjectPHARMACOGENETICS
dc.subjectMERCAPTOPURINE
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleSplit-dose administration of thiopurine drugs: a novel and effective strategy for managing preferential 6-MMP metabolism
dc.typeartículo
dc.volumen36
sipa.codpersvinculados135641
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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