• 作者：M. Á ; lvarez Beltran ; ^{alvarezbeltran@hotmail.com} ; D. Infante Pina ; R. Tormo Carnicé ; O. Segarra Cantó ; n ; S. Redecillas Ferreiro
• 关键词：Azatioprina ; Tiopurina metiltransferasa ; 6-tioguanina ; 6-metilmercaptopurina ; Enfermedad inflamatoria intestinal ; Hepatitis autoinmune ; Metabolitos tiopurí ; nicos
• 刊名：Anales de Pediatr铆a
• 出版年：2009
• 期刊代码：pca47_16954033
• 类别：med
• 出版时间：February 2009
• 卷：70
• 期：2
• 页码：126-131
• 文件大小：607 K

Introduction

Individualised doses of azathioprine (AZA) may be prescribed by monitoring the levels of the enzyme thiopurine methyltransferase (TPMT). The measurements of thiopurine metabolites of AZA, 6-thioguanine (6-TGN) and 6-methylmercaptopurine (6-MMP), have also been reported as new markers of AZA activity.

Objectives

To describe TPMT phenotype in our population and to establish a relationship between thiopurine metabolites,and therapeutic activity and adverse effects.

Material and methods

Data on TPMT were retrospectively collected from 107 patients, and 6-TGN and 6-MMP levels in 18 patients currently on treatment with AZA (Crohn's disease 5, ulcerative colitis 5, autoimmune hepatitis 5).

Results

Mean value of TPMT was 20.19 U/ml. None of the patients had a TPMT activity<5 U/ml. Of the 18 patients on treatment, 13 showed sub-therapeutic levels of 6-TGN (<235 pmol/8脳10⁸ red blood cells). Clinical remission was maintained in 45%of patients. Mean levels of 6-TGN in patients with clinical remission were 259 pmol/8脳10⁸ red blood cells versus 209 pmol/8脳10⁸ red blood cells in non-responders (p=0.37). There was an inverse relationship (r=鈭?.28) between TPMT and 6-TGN levels. Toxic effects occurred in 6 of 18 patients, with leukopenia in 5 and hyperamylasemia in 1.

Conclusions

Determination of TPMT and monitoring of thiopurine metabolites allows AZA treatment to be optimised, although further studies are necessary to establish therapeutic effectiveness and toxicity ranges.