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

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...

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Bibliographic Details
Published in:Alimentary pharmacology & therapeutics 2012-09, Vol.36 (5), p.449-458
Main Authors: Shih, D. Q., Nguyen, M., Zheng, L., Ibanez, P., Mei, L., Kwan, L. Y., Bradford, K., Ting, C., Targan, S. R., Vasiliauskas, E. A.
Format: Article
Language:English
Subjects:
Adolescent
Adult
Azathioprine - administration & dosage
Biological and medical sciences
Digestive system
Dose-Response Relationship, Drug
Erythrocytes - drug effects
Erythrocytes - metabolism
Female
Gastroenterology. Liver. Pancreas. Abdomen
Humans
Immunosuppressive Agents - administration & dosage
Inflammatory Bowel Diseases - drug therapy
Inflammatory Bowel Diseases - metabolism
Male
Medical sciences
Mercaptopurine - administration & dosage
Mercaptopurine - analogs & derivatives
Mercaptopurine - metabolism
Middle Aged
Pharmacology. Drug treatments
Retrospective Studies
Treatment Outcome
Young Adult
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Summary: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 
ISSN:0269-2813
1365-2036
DOI:10.1111/j.1365-2036.2012.05206.x