Safe treatment of thiopurine S-methyltransferase deficient Crohn's disease patients with azathioprine

被引：115

作者：

Kaskas, BA

Louis, E

Hindorf, U

Schaeffeler, E

Deflandre, J

Graepler, F

Schmiegelow, K

Gregor, M

Zanger, UM

Eichelbaum, M

Schwab, M

机构：

[1] Univ Hosp Liege, Dept Gastroenterol, Liege, Belgium

[2] Blekinge Hosp, Dept Internal Med, Karlskrona, Sweden

[3] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-7000 Stuttgart, Germany

[4] Reg Hosp Citadelle, Dept Gastroenterol, Liege, Belgium

[5] Natl Hosp, Juliane Marie Ctr, Dept Pediat 2, Copenhagen, Denmark

[6] Univ Tubingen Hosp, Dept Gastroenterol, Tubingen, Germany

来源：

GUT | 2003年 / 52卷 / 01期

关键词：

D O I：

10.1136/gut.52.1.140

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Thiopurine S-methyltransferase (TPMT) deficient patients develop life threatening haematoxicity (for example, pancytopenia) when treated with a standard dose of azathioprine (AZA) and 6-mercaptopurine (6-MP) due to excessive accumulation of cytotoxic metabolites. At present, it is generally recommended that these patients should not receive AZA or 6-MP treatment for inflammatory bowel disease. We report for the first time that Crohn's disease patients with TPMT deficiency can be successfully treated with AZA. We illustrate this with three cases where treatment has been successful and toxicity has been avoided by carefully titrating the drug dose. Thus very low TPMT activity demands pharmacogenetically guided dosing.

引用

收藏

页码：140 / 142

页数：3

相关论文

共 20 条

[1] Pharmacokinetics, dose adjustments, and 6-mercaptopurine/methotrexate drug interactions in two patients with thiopurine methyltransferase deficiency [J].

Andersen, JB ;

Szumlanski, C ;

Weinshilboum, RM ;

Schmiegelow, K .

ACTA PAEDIATRICA, 1998, 87 (01) :108-111

[2] 6-Thioguanine: A naked bullet? (or how pharmacogenomics can make old drugs brand new) [J].

Baert, F ;

Rutgeerts, P .

INFLAMMATORY BOWEL DISEASES, 2001, 7 (03) :190-191

[3] Therapeutic drug monitoring of azathioprine and 6-mercaptopurine metabolites in Crohn disease [J].

Belaiche, J ;

Desager, JP ;

Horsmans, Y ;

Louis, E .

SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY, 2001, 36 (01) :71-76

[4] 6-MERCAPTOPURINE - CYTOTOXICITY AND BIOCHEMICAL PHARMACOLOGY IN HUMAN-MALIGNANT T-LYMPHOBLASTS [J].

BOKKERINK, JPM ;

STET, EH ;

DEABREU, RA ;

DAMEN, FJM ;

HULSCHER, TW ;

BAKKER, MAH ;

VANBAAL, JA .

BIOCHEMICAL PHARMACOLOGY, 1993, 45 (07) :1455-1463

[5] Utilisation of erythrocyte 6-thioguanine metabolite levels to optimise azathioprine therapy in patients with inflammatory bowel disease [J].

Cuffari, C ;

Hunt, S ;

Bayless, T .

GUT, 2001, 48 (05) :642-646

[6] Pharmacogenomics and metabolite measurement for 6-mercaptopurine therapy in inflammatory bowel disease [J].

Dubinsky, MC ;

Lamothe, S ;

Yang, HY ;

Targan, SR ;

Sinnett, D ;

Théorêt, Y ;

Seidman, EG .

GASTROENTEROLOGY, 2000, 118 (04) :705-713

[7] An open-label pilot study using thioguanine as a therapeutic alternative in Crohn's disease patients resistant to 6-mercaptopurine therapy [J].

Dubinsky, MC ;

Hassard, PV ;

Seidman, EG ;

Kam, LY ;

Abreu, MT ;

Targan, SR ;

Vasiliauskas, EA .

INFLAMMATORY BOWEL DISEASES, 2001, 7 (03) :181-189

[8] Pharmacogenomics: Translating functional genomics into rational therapeutics [J].

Evans, WE ;

Relling, MV .

SCIENCE, 1999, 286 (5439) :487-491

[9] ALTERED MERCAPTOPURINE METABOLISM, TOXIC EFFECTS, AND DOSAGE REQUIREMENT IN A THIOPURINE METHYLTRANSFERASE-DEFICIENT CHILD WITH ACUTE LYMPHOCYTIC-LEUKEMIA [J].

EVANS, WE ;

HORNER, M ;

CHU, YQ ;

KALWINSKY, D ;

ROBERTS, WM .

JOURNAL OF PEDIATRICS, 1991, 119 (06) :985-989

[10] A simple classification of Crohn's disease: Report of the Working Party for the world congresses of gastroenterology, Vienna 1998 [J].

Gasche, C ;

Scholmerich, J ;

Brynskov, J ;

D'Haens, G ;

Hanauer, SB ;

Irvine, EJ ;

Jewell, DP ;

Rachmilewitz, D ;

Sachar, DB ;

Sandborn, WJ ;

Sutherland, LR .

INFLAMMATORY BOWEL DISEASES, 2000, 6 (01) :8-15