共 60 条
Azathioprine and 6-mercaptopurine pharmacogenetics and metabolite monitoring in inflammatory bowel disease
被引:197
作者:

Gearry, RB
论文数: 0 引用数: 0
h-index: 0
机构: Christchurch Hosp, Dept Gastroenterol, Christchurch, New Zealand

Barclay, ML
论文数: 0 引用数: 0
h-index: 0
机构: Christchurch Hosp, Dept Gastroenterol, Christchurch, New Zealand
机构:
[1] Christchurch Hosp, Dept Gastroenterol, Christchurch, New Zealand
[2] Christchurch Hosp, Dept Clin Pharmacol, Christchurch, New Zealand
[3] Christchurch Sch Med & Hlth Sci, Christchurch, New Zealand
关键词:
azathioprine;
efficacy;
inflammatory bowel disease;
6-mercaptopurine;
metabolite monitoring;
pharmacogenetics;
toxicity;
TPMT;
D O I:
10.1111/j.1440-1746.2005.03832.x
中图分类号:
R57 [消化系及腹部疾病];
学科分类号:
摘要:
The thiopurine drugs azathioprine and 6-mercaptopurine (6-MP) are well-established in the treatment of inflammatory bowel disease (IBD). However, there is a wide inter-and intra-patient variation in the concentrations of active and toxic metabolites due to their complex metabolism and genetic polymorphisms in metabolizing enzymes. Serious drug toxicity leads to cessation of therapy in 9-25% of patients, and there is failure to achieve efficacy in approximately 15% of cases. Advances in the understanding of thiopurine drug metabolism have led to new genetic and metabolite tests to help clinicians optimize thiopurine use. Thiopurine methyltransferase (TPMT) enzyme activity can predict life-threatening myelotoxicity in the one in 300 patients who are TPMT-deficient. However, myelotoxicity can also occur in the presence of norma TPMT activity so blood count monitoring should remain standard practice. TPMT testing may also aid in dose individualization. 6-Thioguanine nucleotides (6-TGN) are thought to be the predominant active metabolites of the thiopurines. 6-Thioguanine nucleotide concentration is correlated with bone marrow toxicity and may also correlate with efficacy in IBD. Measurement of 6-TGN and 6-methylmercaptopurine (6-MMP) concentration is most useful in determining why a patient is not responding to a standard dose of a thiopurine drug and may help in avoiding myelosuppression. The ratio of these metabolites can help distinguish non-compliance, under-dosing, thiopurine-resistant and thiopurine-refractory disease. Some of these investigations are entering routine clinical practice but more research is required to determine their optimal use in patients with IBD. (C) 2005 Blackwell Publishing Asia Pty Ltd.
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页码:1149 / 1157
页数:9
相关论文
共 60 条
[11]
Genotypic analysis of thiopurine S-methyltransferase in patients with Crohn's disease and severe myelosuppression during azathioprine therapy
[J].
Colombel, JF
;
Ferrari, N
;
Debuysere, H
;
Marteau, P
;
Gendre, JP
;
Bonaz, B
;
Soulé, JC
;
Modgliani, R
;
Touze, Y
;
Catala, P
;
Libersa, C
;
Broly, F
.
GASTROENTEROLOGY,
2000, 118 (06)
:1025-1030

Colombel, JF
论文数: 0 引用数: 0
h-index: 0
机构: Ctr Hosp Reg & Univ Lille, Hop Huriez, Clin Malad Apparell Digest & Nutr, Serv Hepato Gastroenterol, F-59037 Lille, France

Ferrari, N
论文数: 0 引用数: 0
h-index: 0
机构: Ctr Hosp Reg & Univ Lille, Hop Huriez, Clin Malad Apparell Digest & Nutr, Serv Hepato Gastroenterol, F-59037 Lille, France

Debuysere, H
论文数: 0 引用数: 0
h-index: 0
机构: Ctr Hosp Reg & Univ Lille, Hop Huriez, Clin Malad Apparell Digest & Nutr, Serv Hepato Gastroenterol, F-59037 Lille, France

Marteau, P
论文数: 0 引用数: 0
h-index: 0
机构: Ctr Hosp Reg & Univ Lille, Hop Huriez, Clin Malad Apparell Digest & Nutr, Serv Hepato Gastroenterol, F-59037 Lille, France

Gendre, JP
论文数: 0 引用数: 0
h-index: 0
机构: Ctr Hosp Reg & Univ Lille, Hop Huriez, Clin Malad Apparell Digest & Nutr, Serv Hepato Gastroenterol, F-59037 Lille, France

Bonaz, B
论文数: 0 引用数: 0
h-index: 0
机构: Ctr Hosp Reg & Univ Lille, Hop Huriez, Clin Malad Apparell Digest & Nutr, Serv Hepato Gastroenterol, F-59037 Lille, France

Soulé, JC
论文数: 0 引用数: 0
h-index: 0
机构: Ctr Hosp Reg & Univ Lille, Hop Huriez, Clin Malad Apparell Digest & Nutr, Serv Hepato Gastroenterol, F-59037 Lille, France

Modgliani, R
论文数: 0 引用数: 0
h-index: 0
机构: Ctr Hosp Reg & Univ Lille, Hop Huriez, Clin Malad Apparell Digest & Nutr, Serv Hepato Gastroenterol, F-59037 Lille, France

Touze, Y
论文数: 0 引用数: 0
h-index: 0
机构: Ctr Hosp Reg & Univ Lille, Hop Huriez, Clin Malad Apparell Digest & Nutr, Serv Hepato Gastroenterol, F-59037 Lille, France

Catala, P
论文数: 0 引用数: 0
h-index: 0
机构: Ctr Hosp Reg & Univ Lille, Hop Huriez, Clin Malad Apparell Digest & Nutr, Serv Hepato Gastroenterol, F-59037 Lille, France

Libersa, C
论文数: 0 引用数: 0
h-index: 0
机构: Ctr Hosp Reg & Univ Lille, Hop Huriez, Clin Malad Apparell Digest & Nutr, Serv Hepato Gastroenterol, F-59037 Lille, France

Broly, F
论文数: 0 引用数: 0
h-index: 0
机构: Ctr Hosp Reg & Univ Lille, Hop Huriez, Clin Malad Apparell Digest & Nutr, Serv Hepato Gastroenterol, F-59037 Lille, France
[12]
The relationship between thiopurine methyltransferase activity and genotype in blasts from patients with acute leukemia
[J].
Coulthard, SA
;
Howell, C
;
Robson, J
;
Hall, AG
.
BLOOD,
1998, 92 (08)
:2856-2862

Coulthard, SA
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Newcastle Upon Tyne, Sch Med, Canc Res Unit, LRF Mol Pharmacol Specialist Programme,LRF Grp, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England Univ Newcastle Upon Tyne, Sch Med, Canc Res Unit, LRF Mol Pharmacol Specialist Programme,LRF Grp, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England

Howell, C
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Newcastle Upon Tyne, Sch Med, Canc Res Unit, LRF Mol Pharmacol Specialist Programme,LRF Grp, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England Univ Newcastle Upon Tyne, Sch Med, Canc Res Unit, LRF Mol Pharmacol Specialist Programme,LRF Grp, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England

Robson, J
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Newcastle Upon Tyne, Sch Med, Canc Res Unit, LRF Mol Pharmacol Specialist Programme,LRF Grp, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England Univ Newcastle Upon Tyne, Sch Med, Canc Res Unit, LRF Mol Pharmacol Specialist Programme,LRF Grp, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England

Hall, AG
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Newcastle Upon Tyne, Sch Med, Canc Res Unit, LRF Mol Pharmacol Specialist Programme,LRF Grp, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England Univ Newcastle Upon Tyne, Sch Med, Canc Res Unit, LRF Mol Pharmacol Specialist Programme,LRF Grp, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England
[13]
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

Cuffari, C
论文数: 0 引用数: 0
h-index: 0
机构: Johns Hopkins Univ Hosp, Dept Pediat, Div Gastroenterol, Baltimore, MD 21287 USA

Hunt, S
论文数: 0 引用数: 0
h-index: 0
机构: Johns Hopkins Univ Hosp, Dept Pediat, Div Gastroenterol, Baltimore, MD 21287 USA

Bayless, T
论文数: 0 引用数: 0
h-index: 0
机构: Johns Hopkins Univ Hosp, Dept Pediat, Div Gastroenterol, Baltimore, MD 21287 USA
[14]
6-Mercaptopurine metabolism in Crohn's disease: Correlation with efficacy and toxicity
[J].
Cuffari, C
;
Theoret, Y
;
Latour, S
;
Seidman, G
.
GUT,
1996, 39 (03)
:401-406

Cuffari, C
论文数: 0 引用数: 0
h-index: 0
机构: UNIV MONTREAL,DIV PEDIAT GASTROENTEROL,HOP ST JUSTINE,DEPT PEDIAT,CTR RECH,MONTREAL,PQ H3T 1C5,CANADA

Theoret, Y
论文数: 0 引用数: 0
h-index: 0
机构: UNIV MONTREAL,DIV PEDIAT GASTROENTEROL,HOP ST JUSTINE,DEPT PEDIAT,CTR RECH,MONTREAL,PQ H3T 1C5,CANADA

Latour, S
论文数: 0 引用数: 0
h-index: 0
机构: UNIV MONTREAL,DIV PEDIAT GASTROENTEROL,HOP ST JUSTINE,DEPT PEDIAT,CTR RECH,MONTREAL,PQ H3T 1C5,CANADA

Seidman, G
论文数: 0 引用数: 0
h-index: 0
机构: UNIV MONTREAL,DIV PEDIAT GASTROENTEROL,HOP ST JUSTINE,DEPT PEDIAT,CTR RECH,MONTREAL,PQ H3T 1C5,CANADA
[15]
Genotypic and phenotypic analysis of the polymorphic thiopurine S-methyltransferase gene (TPMT) in a European population
[J].
de la Moureyre, CSV
;
Debuysere, H
;
Mastain, B
;
Vinner, E
;
Marez, D
;
Lo Guidice, JM
;
Chevalier, D
;
Brique, S
;
Motte, K
;
Colombel, JF
;
Turck, D
;
Noel, C
;
Flipo, RM
;
Pol, A
;
Lhermitte, M
;
Lafitte, JJ
;
Libersa, C
;
Broly, F
.
BRITISH JOURNAL OF PHARMACOLOGY,
1998, 125 (04)
:879-887

de la Moureyre, CSV
论文数: 0 引用数: 0
h-index: 0
机构: Ctr Hosp Reg & Univ Lille, Lab Biochim & Biol Mol, Hop Calmette, F-59037 Lille, France

Debuysere, H
论文数: 0 引用数: 0
h-index: 0
机构: Ctr Hosp Reg & Univ Lille, Lab Biochim & Biol Mol, Hop Calmette, F-59037 Lille, France

Mastain, B
论文数: 0 引用数: 0
h-index: 0
机构: Ctr Hosp Reg & Univ Lille, Lab Biochim & Biol Mol, Hop Calmette, F-59037 Lille, France

Vinner, E
论文数: 0 引用数: 0
h-index: 0
机构: Ctr Hosp Reg & Univ Lille, Lab Biochim & Biol Mol, Hop Calmette, F-59037 Lille, France

Marez, D
论文数: 0 引用数: 0
h-index: 0
机构: Ctr Hosp Reg & Univ Lille, Lab Biochim & Biol Mol, Hop Calmette, F-59037 Lille, France

Lo Guidice, JM
论文数: 0 引用数: 0
h-index: 0
机构: Ctr Hosp Reg & Univ Lille, Lab Biochim & Biol Mol, Hop Calmette, F-59037 Lille, France

Chevalier, D
论文数: 0 引用数: 0
h-index: 0
机构: Ctr Hosp Reg & Univ Lille, Lab Biochim & Biol Mol, Hop Calmette, F-59037 Lille, France

Brique, S
论文数: 0 引用数: 0
h-index: 0
机构: Ctr Hosp Reg & Univ Lille, Lab Biochim & Biol Mol, Hop Calmette, F-59037 Lille, France

Motte, K
论文数: 0 引用数: 0
h-index: 0
机构: Ctr Hosp Reg & Univ Lille, Lab Biochim & Biol Mol, Hop Calmette, F-59037 Lille, France

Colombel, JF
论文数: 0 引用数: 0
h-index: 0
机构: Ctr Hosp Reg & Univ Lille, Lab Biochim & Biol Mol, Hop Calmette, F-59037 Lille, France

Turck, D
论文数: 0 引用数: 0
h-index: 0
机构: Ctr Hosp Reg & Univ Lille, Lab Biochim & Biol Mol, Hop Calmette, F-59037 Lille, France

Noel, C
论文数: 0 引用数: 0
h-index: 0
机构: Ctr Hosp Reg & Univ Lille, Lab Biochim & Biol Mol, Hop Calmette, F-59037 Lille, France

Flipo, RM
论文数: 0 引用数: 0
h-index: 0
机构: Ctr Hosp Reg & Univ Lille, Lab Biochim & Biol Mol, Hop Calmette, F-59037 Lille, France

Pol, A
论文数: 0 引用数: 0
h-index: 0
机构: Ctr Hosp Reg & Univ Lille, Lab Biochim & Biol Mol, Hop Calmette, F-59037 Lille, France

Lhermitte, M
论文数: 0 引用数: 0
h-index: 0
机构: Ctr Hosp Reg & Univ Lille, Lab Biochim & Biol Mol, Hop Calmette, F-59037 Lille, France

Lafitte, JJ
论文数: 0 引用数: 0
h-index: 0
机构: Ctr Hosp Reg & Univ Lille, Lab Biochim & Biol Mol, Hop Calmette, F-59037 Lille, France

Libersa, C
论文数: 0 引用数: 0
h-index: 0
机构: Ctr Hosp Reg & Univ Lille, Lab Biochim & Biol Mol, Hop Calmette, F-59037 Lille, France

Broly, F
论文数: 0 引用数: 0
h-index: 0
机构: Ctr Hosp Reg & Univ Lille, Lab Biochim & Biol Mol, Hop Calmette, F-59037 Lille, France
[16]
Optimizing immunomodulator therapy for inflammatory bowel disease
[J].
Marla C. Dubinsky
.
Current Gastroenterology Reports,
2003, 5 (6)
:506-511

Marla C. Dubinsky
论文数: 0 引用数: 0
h-index: 0
机构: Pediatric IBD Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048
[17]
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

Dubinsky, MC
论文数: 0 引用数: 0
h-index: 0
机构: Univ Montreal, Hop St Justine, Div Gastroenterol & Nutr, Montreal, PQ H3T 1C5, Canada

Lamothe, S
论文数: 0 引用数: 0
h-index: 0
机构: Univ Montreal, Hop St Justine, Div Gastroenterol & Nutr, Montreal, PQ H3T 1C5, Canada

Yang, HY
论文数: 0 引用数: 0
h-index: 0
机构: Univ Montreal, Hop St Justine, Div Gastroenterol & Nutr, Montreal, PQ H3T 1C5, Canada

Targan, SR
论文数: 0 引用数: 0
h-index: 0
机构: Univ Montreal, Hop St Justine, Div Gastroenterol & Nutr, Montreal, PQ H3T 1C5, Canada

Sinnett, D
论文数: 0 引用数: 0
h-index: 0
机构: Univ Montreal, Hop St Justine, Div Gastroenterol & Nutr, Montreal, PQ H3T 1C5, Canada

Théorêt, Y
论文数: 0 引用数: 0
h-index: 0
机构: Univ Montreal, Hop St Justine, Div Gastroenterol & Nutr, Montreal, PQ H3T 1C5, Canada

Seidman, EG
论文数: 0 引用数: 0
h-index: 0
机构: Univ Montreal, Hop St Justine, Div Gastroenterol & Nutr, Montreal, PQ H3T 1C5, Canada
[18]
6-thioguanine can cause serious liver injury in inflammatory bowel disease patients
[J].
Dubinsky, MC
;
Vasiliauskas, EA
;
Singh, H
;
Abreu, MT
;
Papadakis, KA
;
Tran, T
;
Martin, P
;
Vierling, JM
;
Geller, SA
;
Targan, SR
;
Poordad, FF
.
GASTROENTEROLOGY,
2003, 125 (02)
:298-303

Dubinsky, MC
论文数: 0 引用数: 0
h-index: 0
机构: Cedars Sinai Med Ctr, Dept Pediat, Div Gastroenterol & Hepatol, Pediat Inflammatory Bowel Dis Ctr, Los Angeles, CA 90048 USA

Vasiliauskas, EA
论文数: 0 引用数: 0
h-index: 0
机构: Cedars Sinai Med Ctr, Dept Pediat, Div Gastroenterol & Hepatol, Pediat Inflammatory Bowel Dis Ctr, Los Angeles, CA 90048 USA

Singh, H
论文数: 0 引用数: 0
h-index: 0
机构: Cedars Sinai Med Ctr, Dept Pediat, Div Gastroenterol & Hepatol, Pediat Inflammatory Bowel Dis Ctr, Los Angeles, CA 90048 USA

Abreu, MT
论文数: 0 引用数: 0
h-index: 0
机构: Cedars Sinai Med Ctr, Dept Pediat, Div Gastroenterol & Hepatol, Pediat Inflammatory Bowel Dis Ctr, Los Angeles, CA 90048 USA

Papadakis, KA
论文数: 0 引用数: 0
h-index: 0
机构: Cedars Sinai Med Ctr, Dept Pediat, Div Gastroenterol & Hepatol, Pediat Inflammatory Bowel Dis Ctr, Los Angeles, CA 90048 USA

Tran, T
论文数: 0 引用数: 0
h-index: 0
机构: Cedars Sinai Med Ctr, Dept Pediat, Div Gastroenterol & Hepatol, Pediat Inflammatory Bowel Dis Ctr, Los Angeles, CA 90048 USA

Martin, P
论文数: 0 引用数: 0
h-index: 0
机构: Cedars Sinai Med Ctr, Dept Pediat, Div Gastroenterol & Hepatol, Pediat Inflammatory Bowel Dis Ctr, Los Angeles, CA 90048 USA

Vierling, JM
论文数: 0 引用数: 0
h-index: 0
机构: Cedars Sinai Med Ctr, Dept Pediat, Div Gastroenterol & Hepatol, Pediat Inflammatory Bowel Dis Ctr, Los Angeles, CA 90048 USA

Geller, SA
论文数: 0 引用数: 0
h-index: 0
机构: Cedars Sinai Med Ctr, Dept Pediat, Div Gastroenterol & Hepatol, Pediat Inflammatory Bowel Dis Ctr, Los Angeles, CA 90048 USA

Targan, SR
论文数: 0 引用数: 0
h-index: 0
机构: Cedars Sinai Med Ctr, Dept Pediat, Div Gastroenterol & Hepatol, Pediat Inflammatory Bowel Dis Ctr, Los Angeles, CA 90048 USA

Poordad, FF
论文数: 0 引用数: 0
h-index: 0
机构: Cedars Sinai Med Ctr, Dept Pediat, Div Gastroenterol & Hepatol, Pediat Inflammatory Bowel Dis Ctr, Los Angeles, CA 90048 USA
[19]
Thioguanine: A potential alternate thiopurine for IBD patients allergic to 6-mercaptopurine or azathioprine
[J].
Dubinsky, MC
;
Feldman, EJ
;
Abreu, MT
;
Targan, SR
;
Vasiliauskas, EA
.
AMERICAN JOURNAL OF GASTROENTEROLOGY,
2003, 98 (05)
:1058-1063

Dubinsky, MC
论文数: 0 引用数: 0
h-index: 0
机构: Univ Calif Los Angeles, Cedars Sinai Med Ctr, Pediat Inflammatory Bowel Dis Ctr, Div Gastroenterol,Dept Med, Los Angeles, CA 90048 USA

Feldman, EJ
论文数: 0 引用数: 0
h-index: 0
机构: Univ Calif Los Angeles, Cedars Sinai Med Ctr, Pediat Inflammatory Bowel Dis Ctr, Div Gastroenterol,Dept Med, Los Angeles, CA 90048 USA

Abreu, MT
论文数: 0 引用数: 0
h-index: 0
机构: Univ Calif Los Angeles, Cedars Sinai Med Ctr, Pediat Inflammatory Bowel Dis Ctr, Div Gastroenterol,Dept Med, Los Angeles, CA 90048 USA

Targan, SR
论文数: 0 引用数: 0
h-index: 0
机构: Univ Calif Los Angeles, Cedars Sinai Med Ctr, Pediat Inflammatory Bowel Dis Ctr, Div Gastroenterol,Dept Med, Los Angeles, CA 90048 USA

Vasiliauskas, EA
论文数: 0 引用数: 0
h-index: 0
机构: Univ Calif Los Angeles, Cedars Sinai Med Ctr, Pediat Inflammatory Bowel Dis Ctr, Div Gastroenterol,Dept Med, Los Angeles, CA 90048 USA
[20]
6-MP metabolite profiles provide a biochemical explanation for 6-MP resistance in patients with inflammatory bowel disease
[J].
Dubinsky, MC
;
Yang, HY
;
Hassard, PV
;
Seidman, EG
;
Kam, LY
;
Abreu, MT
;
Targan, SR
;
Vasiliauskas, EA
.
GASTROENTEROLOGY,
2002, 122 (04)
:904-915

Dubinsky, MC
论文数: 0 引用数: 0
h-index: 0
机构: Univ Calif Los Angeles, Cedars Sinai Med Ctr, Ctr Inflammatory Bowel Dis, Div Gastroenterol, Los Angeles, CA 90048 USA

Yang, HY
论文数: 0 引用数: 0
h-index: 0
机构: Univ Calif Los Angeles, Cedars Sinai Med Ctr, Ctr Inflammatory Bowel Dis, Div Gastroenterol, Los Angeles, CA 90048 USA

Hassard, PV
论文数: 0 引用数: 0
h-index: 0
机构: Univ Calif Los Angeles, Cedars Sinai Med Ctr, Ctr Inflammatory Bowel Dis, Div Gastroenterol, Los Angeles, CA 90048 USA

Seidman, EG
论文数: 0 引用数: 0
h-index: 0
机构: Univ Calif Los Angeles, Cedars Sinai Med Ctr, Ctr Inflammatory Bowel Dis, Div Gastroenterol, Los Angeles, CA 90048 USA

Kam, LY
论文数: 0 引用数: 0
h-index: 0
机构: Univ Calif Los Angeles, Cedars Sinai Med Ctr, Ctr Inflammatory Bowel Dis, Div Gastroenterol, Los Angeles, CA 90048 USA

Abreu, MT
论文数: 0 引用数: 0
h-index: 0
机构: Univ Calif Los Angeles, Cedars Sinai Med Ctr, Ctr Inflammatory Bowel Dis, Div Gastroenterol, Los Angeles, CA 90048 USA

Targan, SR
论文数: 0 引用数: 0
h-index: 0
机构: Univ Calif Los Angeles, Cedars Sinai Med Ctr, Ctr Inflammatory Bowel Dis, Div Gastroenterol, Los Angeles, CA 90048 USA

Vasiliauskas, EA
论文数: 0 引用数: 0
h-index: 0
机构: Univ Calif Los Angeles, Cedars Sinai Med Ctr, Ctr Inflammatory Bowel Dis, Div Gastroenterol, Los Angeles, CA 90048 USA