Optimising azathioprine treatment: determination of thiopurine methyltransferase activity and thiopurine metabolites

• Published in: Anales de pediatría (Barcelona, Spain : 2003) Vol. 70; no. 2; p. 126
• Main Authors: Alvarez Beltran, M, Infante Pina, D, Tormo Carnicé, R, Segarra Cantón, O, Redecillas Ferreiro, S
• Format: Journal Article
• Language: Spanish
• Published: Spain 01.02.2009
• Subjects: Adolescent; Azathioprine - administration & dosage; Female; Hepatitis, Autoimmune - drug therapy; Hepatitis, Autoimmune - enzymology; Hepatitis, Autoimmune - metabolism; Humans; Immunosuppressive Agents - administration & dosage; Inflammatory Bowel Diseases - drug therapy; Inflammatory Bowel Diseases - enzymology; Inflammatory Bowel Diseases - metabolism; Male; Mercaptopurine - analogs & derivatives; Mercaptopurine - metabolism; Methyltransferases - metabolism; Retrospective Studies; Thioguanine - metabolism
• ISSN: 1695-4033
• DOI: 10.1016/j.anpedi.2008.10.010

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. To describe TPMT phenotype in our population and to establish a relationship between thiopurine metabolites,and therapeutic activity and adverse effects. 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). Mean value of TPMT was 20.19U/ml. None of the patients had a TPMT activity<5U/ml. Of the 18 patients on treatment, 13 showed sub-therapeutic levels of 6-TGN (<235pmol/8x10(8) red blood cells). Clinical remission was maintained in 45% of patients. Mean levels of 6-TGN in patients with clinical remission were 259pmol/8x10(8) red blood cells versus 209pmol/8x10(8) red blood cells in non-responders (p=0.37). There was an inverse relationship (r=-0.28) between TPMT and 6-TGN levels. Toxic effects occurred in 6 of 18 patients, with leukopenia in 5 and hyperamylasemia in 1. 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.