Thiopurine methyltransferase and thiopurine metabolite testing in patients with inflammatory bowel disease who are taking thiopurine drugs

被引:8
|
作者
Sheffield, Leslie J. [1 ,2 ]
Irving, Peter [3 ]
Gupta, Arun [4 ]
Byron, Keith [5 ]
Macrae, Finlay A. [4 ]
Phillimore, Hazel [2 ]
Dronavalli, Mithilesh [6 ,7 ]
Rose, Rosemary [3 ]
George, Peter [8 ]
Walmsley, Trevor [8 ]
Dixon, Barbara [9 ]
Poole, Susan [9 ]
Dooley, Michael [9 ,10 ]
Sparrow, Miles [3 ,9 ]
机构
[1] Murdoch Childrens Res Inst, Genet Hlth Serv Victoria, Parkville, Vic 3052, Australia
[2] GenesFX Hlth Pty Ltd, Melbourne, Vic, Australia
[3] Box Hill Hosp, Melbourne, Vic, Australia
[4] Univ Melbourne, Royal Melbourne Hosp, Melbourne, Vic 3050, Australia
[5] Gribbles Pathol, Melbourne, Vic, Australia
[6] Univ Melbourne, Melbourne, Vic, Australia
[7] Data Clin, Quakers Hill, Australia
[8] Canterbury Hlth Labs, Christchurch, New Zealand
[9] Alfred Hlth, Melbourne, Vic, Australia
[10] Monash Univ, Melbourne, Vic 3004, Australia
关键词
6-mercaptopurine; 6-methylmercaptopurine; 6-thioguanine nucleotides; azathioprine; dosage; extensive metabolizer; intermediate metabolizer; thiopurine drugs; thiopurine methyltransferase testing; TPMT; 6-MERCAPTOPURINE THERAPY; AZATHIOPRINE; PHARMACOGENETICS; EXPLANATION; TPMT;
D O I
10.2217/PGS.09.60
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Thiopurine methyltransferase genotyping and thiopurine metabolite testing has been established as an adjunct to monitoring patients taking thiopurine drugs. This special report describes the clinical implications for this type of testing for patients with inflammatory bowel disease who are taking thiopurine drugs. A total of 10% of patients were found to be intermediate metabolizers and the mean dosage (in mg/kg equivalent) was lower in intermediate metabolizers than extensive metabolizers. The metabolite levels did not correlate with scores measuring clinical severity but levels of 6-methylmercaptopurine were related to the dosage of the drugs. Despite considerable study of thiopurine methyltransferase testing in the literature, it is still not widely used in many geographical areas. This study adds to the evidence about using such testing as well as expanding the role of simultaneously measuring thiopurine metabolites. Further work is planned to evaluate the uptake when such testing becomes available locally as a clinical service.
引用
收藏
页码:1091 / 1099
页数:9
相关论文
共 50 条
  • [21] The effect of thiopurine methyltransferase on the cytotoxic action of thiopurine drugs
    Hogarth, LA
    Coulthard, SA
    Hall, AG
    Skitt, L
    LEUKEMIA, 2003, 17 (03) : 665 - 665
  • [22] Thiopurine Methyltransferase Gene Polymorphisms in Chinese Patients with Inflammatory Bowel Disease
    Cao, Qian
    Zhu, Qin
    Shang, Yan
    Gao, Min
    Si, Jianmin
    DIGESTION, 2009, 79 (01) : 58 - 63
  • [23] The effect of thiopurine methyltransferase expression on sensitivity to thiopurine drugs
    Coulthard, SA
    Hogarth, LA
    Little, M
    Matheson, EC
    Redfern, CPF
    Minto, L
    Hall, AG
    MOLECULAR PHARMACOLOGY, 2002, 62 (01) : 102 - 109
  • [24] Thiopurine S-methyltransferase polymorphisms: efficient screening method for patients considering taking thiopurine drugs
    Barbara Wusk
    G. A. Kullak-Ublick
    C. Rammert
    A. von Eckardstein
    M. Fried
    K. M. Rentsch
    European Journal of Clinical Pharmacology, 2004, 60 : 5 - 10
  • [25] Thiopurine S-methyltransferase polymorphisms:: efficient screening method for patients considering taking thiopurine drugs
    Wusk, B
    Kullak-Ublick, GA
    Rammert, C
    von Eckardstein, A
    Fried, M
    Rentsch, KM
    EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, 2004, 60 (01) : 5 - 10
  • [26] Thiopurine methyltransferase activity and the use of azathioprine in inflammatory bowel disease
    Ansari, A
    Hassan, C
    Duley, J
    Marinaki, A
    Shobowale-Bakre, EM
    Seed, P
    Meenan, J
    Yim, A
    Sanderson, J
    ALIMENTARY PHARMACOLOGY & THERAPEUTICS, 2002, 16 (10) : 1743 - 1750
  • [27] Thiopurine methyltransferase and the metabolism of thiopurine drugs in a large Swedish population
    Hindorf, U
    Almer, S
    Peterson, C
    GASTROENTEROLOGY, 2004, 126 (04) : A212 - A212
  • [28] Characterisation and utility of thiopurine methyltransferase and thiopurine metabolite measurements in autoimmune hepatitis
    Hindorf, Ulf
    Jahed, Khatoon
    Bergquist, Annika
    Verbaan, Hans
    Prytz, Hanne
    Wallerstedt, Sven
    Werner, Marten
    Olsson, Rolf
    Bjoernsson, Einar
    Peterson, Curt
    Almer, Sven H. C.
    JOURNAL OF HEPATOLOGY, 2010, 52 (01) : 106 - 111
  • [29] Measurement of thiopurine methyltransferase activity and azathioprine metabolites in patients with inflammatory bowel disease
    Lowry, PW
    Franklin, CL
    Weaver, AL
    Pike, MG
    Mays, DC
    Tremaine, WJ
    Lipsky, JJ
    Sandborn, WJ
    GUT, 2001, 49 (05) : 665 - 670
  • [30] Thiopurine Treatment in Inflammatory Bowel Disease
    Sharon J. Gardiner
    Evan J. Begg
    Ashis Sau
    Anthony Marinaki
    Richard B. Gearry
    Murray L. Barclay
    Clinical Pharmacokinetics, 2007, 46 : 803 - 804