The role of thiopurine metabolites in inflammatory bowel disease and rheumatological disorders

被引：8

作者：

Friedman, Antony B. ^{[1
]}

Sparrow, Miles P.

Gibson, Peter R.

机构：

[1] Alfred Hosp, Dept Gastroenterol, Melbourne, Vic 3004, Australia

来源：

INTERNATIONAL JOURNAL OF RHEUMATIC DISEASES | 2014年 / 17卷 / 02期

关键词：

6-methymercaptopurine; 6-thioguanine nucleotide; inflammatory bowel disease; thiopurines; 6-THIOGUANINE NUCLEOTIDE; CROHNS-DISEASE; LONG-TERM; METHYLTRANSFERASE ACTIVITY; DOUBLE-BLIND; AZATHIOPRINE METABOLITES; S-METHYLTRANSFERASE; COMBINATION THERAPY; ADVERSE EVENTS; 6-MERCAPTOPURINE;

D O I：

10.1111/1756-185X.12204

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Thiopurines have been a cornerstone of medical management of patients with inflammatory bowel disease (IBD) and many rheumatological disorders. The thiopurines are metabolized to their end products, 6-methymercaptopurine (6MMP) and the 6-thioguanine nucleotides (6TGN), with 6TGN being responsible for thiopurine efficacy by causing apoptosis and preventing activation and proliferation of T-lymphocytes. In IBD, conventional weight-based dosing with thiopurines leads to an inadequate response in many patients. Utilizing measurement of these metabolites and then employing dose optimization strategies has led to markedly improved outcomes in IBD. Switching between thiopurines as well as the addition of low-dose allopurinol can overcome adverse events and elevate 6TGN levels into the therapeutic window. There is a paucity of data on thiopurine metabolites in rheumatological diseases and further research is required.

引用

页码：132 / 141

页数：10

共 78 条

[31] Thiopurine therapies - Problems, complexities, and progress with monitoring thioguanine nucleotides [J].

Duley, John A. ;

Florin, Timothy H. J. .

THERAPEUTIC DRUG MONITORING, 2005, 27 (05) :647-654

[32] Divergent activities of human glutathione transferases in the bioactivation of azathioprine [J].

Eklund, Birgitta I. ;

Moberg, My ;

Bergquist, Jonas ;

Mannervik, Bengt .

MOLECULAR PHARMACOLOGY, 2006, 70 (02) :747-754

[33] CONCURRENT UNILATERAL CHROMATID DAMAGE AND DNA STRAND BREAKAGE IN RESPONSE TO 6-THIOGUANINE TREATMENT [J].

FAIRCHILD, CR ;

MAYBAUM, J ;

KENNEDY, KA .

BIOCHEMICAL PHARMACOLOGY, 1986, 35 (20) :3533-3541

[34] Allopurinol might improve response to azathioprine and 6-mercaptopurine by correcting an unfavorable metabolite ratio [J].

Gardiner, Sharon J. ;

Gearry, Richard B. ;

Burt, Michael J. ;

Chalmers-Watson, Teresa ;

Chapman, Bruce A. ;

Ross, Alison G. ;

Stedman, Catherine A. M. ;

Huelsen, Alexander ;

Barclay, Murray L. .

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 2011, 26 (01) :49-54

[35] A prospective evaluation of the impact of allopurinol in pediatric and adult IBD patients with preferential metabolism of 6-mercaptopurine to 6-methylmercaptopurine [J].

Gerich, Mark E. ;

Quiros, J. Antonio ;

Marcin, James P. ;

Tennyson, Linda ;

Henthorn, Maria ;

Prindiville, Thomas P. .

JOURNAL OF CROHNS & COLITIS, 2010, 4 (05) :546-552

[36] Thiopurine methyl-transferase activity and azathioprine metabolite concentrations do not predict clinical outcome in thiopurine-treated inflammatory bowel disease patients [J].

Gonzalez-Lama, Y. ;

Bermejo, F. ;

Lopez-Sanroman, A. ;

Garcia-Sanchez, V. ;

Esteve, M. ;

Cabriada, J. L. ;

McNicholl, A. G. ;

Pajares, R. ;

Casellas, F. ;

Merino, O. ;

Carpio, D. ;

Vera, M. I. ;

Munoz, C. ;

Calvo, M. ;

Benito, L. M. ;

Bujanda, L. ;

Garcia-Fernandez, F. J. ;

Ricart, E. ;

Ginard, D. ;

Velasco, M. ;

Carneros, J. A. ;

Mancenido, N. ;

Calvo, M. ;

Algaba, A. ;

Froilan, C. ;

Cara, C. ;

Mate, J. ;

Abreu, L. ;

Gisbert, J. P. .

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, 2011, 34 (05) :544-554

[37] Combination of thiopurines and allopurinol: Adverse events and clinical benefit in IBD [J].

Govani, Shail M. ;

Higgins, Peter D. R. .

JOURNAL OF CROHNS & COLITIS, 2010, 4 (04) :444-449

[38] Clinical Usefulness of Therapeutic Drug Monitoring of Thiopurines in Patients with Inadequately Controlled Inflammatory Bowel Disease [J].

Haines, Melissa L. ;

Ajlouni, Yousef ;

Irving, Peter M. ;

Sparrow, Miles P. ;

Rose, Rosemary ;

Gearry, Richard B. ;

Gibson, Peter R. .

INFLAMMATORY BOWEL DISEASES, 2011, 17 (06) :1301-1307

[39] Pharmacogenetics during standardised initiation of thiopurine treatment in inflammatory bowel disease [J].

Hindorf, U. ;

Lindqvist, M. ;

Peterson, C. ;

Soderkvist, P. ;

Strom, M. ;

Hjortswang, H. ;

Pousette, A. ;

Almer, S. .

GUT, 2006, 55 (10) :1423-1431

[40] Adverse events leading to modification of therapy in a large cohort of patients with inflammatory bowel disease [J].

Hindorf, U. ;

Lindqvist, M. ;

Hildebrand, H. ;

Fagerberg, U. ;

Almer, S. .

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, 2006, 24 (02) :331-342

← 1 2 3 4 5 6 7 8 →