[Optimising azathioprine treatment: determination of thiopurine methyltransferase activity and thiopurine metabolites].
BACKGROUND
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.


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


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 20.19U/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.


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.
Alvarez Beltran
M
M
Unidad de Gastroenterología, Hepatología y Soporte Nutricional Pediátrico, Hospital Universitario Vall d'Hebrón, Barcelona, España. alvarezbeltran@hotmail.com
Infante Pina
D
D
Tormo Carnicé
R
R
Segarra Cantón
O
O
Redecillas Ferreiro
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S
D000293:Adolescent; D001379:Azathioprine / Q000008:administration & dosage*; D005260:Female; D019693:Hepatitis, Autoimmune / Q000188:drug therapy* / Q000201:enzymology* / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D015122:Mercaptopurine / Q000031:analogs & derivatives* / Q000378:metabolism; D008780:Methyltransferases / Q000378:metabolism*; D012189:Retrospective Studies; D013866:Thioguanine / Q000378:metabolism*
D007166:Immunosuppressive Agents; C010240:6-methylthiopurine; D015122:Mercaptopurine; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D013866:Thioguanine; D001379:Azathioprine