Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 7-Day Trial for You or Your Team.

Learn More →

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

Split‐dose administration of thiopurine drugs: a novel and effective strategy for managing... Summary 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 × 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 × 108 erythrocytes; P < 0.0001) without negatively affecting clinical disease activity or 6‐TGN levels (239 vs. 216 pmol/8 × 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Alimentary Pharmacology & Therapeutics Wiley

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

Download PDF
10 pages

Loading next page...
 
/lp/wiley/split-dose-administration-of-thiopurine-drugs-a-novel-and-effective-wW3SczVj0b

References (36)

Publisher
Wiley
Copyright
Copyright © 2012 Blackwell Publishing Ltd
ISSN
0269-2813
eISSN
1365-2036
DOI
10.1111/j.1365-2036.2012.05206.x
pmid
22784257
Publisher site
See Article on Publisher Site

Abstract

Summary 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 × 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 × 108 erythrocytes; P < 0.0001) without negatively affecting clinical disease activity or 6‐TGN levels (239 vs. 216 pmol/8 × 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.

Journal

Alimentary Pharmacology & Therapeutics – Wiley

Published: Sep 1, 2012

There are no references for this article.