Split-dose administration of thiopurine drugs: a novel and effective strategy for managing preferential 6-MMP metabolism
dc.contributor.author | Shih, D. Q. | |
dc.contributor.author | Nguyen, M. | |
dc.contributor.author | Zheng, L. | |
dc.contributor.author | Ibanez, P. | |
dc.contributor.author | Mei, L. | |
dc.contributor.author | Kwan, L. Y. | |
dc.contributor.author | Bradford, K. | |
dc.contributor.author | Ting, C. | |
dc.contributor.author | Targan, S. R. | |
dc.contributor.author | Vasiliauskas, E. A. | |
dc.date.accessioned | 2024-01-10T13:43:38Z | |
dc.date.available | 2024-01-10T13:43:38Z | |
dc.date.issued | 2012 | |
dc.description.abstract | Background 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.funder | Cedars-Sinai Medical Center Inflammatory Bowel & Immunobiology Research Institute | |
dc.description.funder | NIH | |
dc.description.funder | NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES | |
dc.fechaingreso.objetodigital | 2024-05-07 | |
dc.format.extent | 10 páginas | |
dc.fuente.origen | WOS | |
dc.identifier.doi | 10.1111/j.1365-2036.2012.05206.x | |
dc.identifier.issn | 0269-2813 | |
dc.identifier.pubmedid | MEDLINE:22784257 | |
dc.identifier.uri | https://doi.org/10.1111/j.1365-2036.2012.05206.x | |
dc.identifier.uri | https://repositorio.uc.cl/handle/11534/78706 | |
dc.identifier.wosid | WOS:000307164600005 | |
dc.information.autoruc | Medicina;Ibañez P ;S/I;135641 | |
dc.issue.numero | 5 | |
dc.language.iso | en | |
dc.nota.acceso | contenido parcial | |
dc.pagina.final | 458 | |
dc.pagina.inicio | 449 | |
dc.publisher | WILEY-BLACKWELL | |
dc.revista | ALIMENTARY PHARMACOLOGY & THERAPEUTICS | |
dc.rights | acceso restringido | |
dc.subject | INFLAMMATORY-BOWEL-DISEASE | |
dc.subject | T-CELL LYMPHOMA | |
dc.subject | CROHNS-DISEASE | |
dc.subject | LONG-TERM | |
dc.subject | METHYLTRANSFERASE ACTIVITY | |
dc.subject | 6-MERCAPTOPURINE THERAPY | |
dc.subject | AZATHIOPRINE THERAPY | |
dc.subject | ALLOPURINOL | |
dc.subject | PHARMACOGENETICS | |
dc.subject | MERCAPTOPURINE | |
dc.subject.ods | 03 Good Health and Well-being | |
dc.subject.odspa | 03 Salud y bienestar | |
dc.title | Split-dose administration of thiopurine drugs: a novel and effective strategy for managing preferential 6-MMP metabolism | |
dc.type | artículo | |
dc.volumen | 36 | |
sipa.codpersvinculados | 135641 | |
sipa.index | WOS | |
sipa.index | Scopus | |
sipa.trazabilidad | Carga SIPA;09-01-2024 |
Files
Original bundle
1 - 1 of 1
Loading...
- Name:
- Split-dose administration of thiopurine drugs a novel and effective strategy for managing preferential 6-MMP metabolism.pdf
- Size:
- 3.34 KB
- Format:
- Adobe Portable Document Format
- Description: