Clinical Pharmacogenetics Implementation Consortium Guidelines for Thiopurine Methyltransferase Genotype and Thiopurine Dosing

被引：399

作者：

Relling, M. V. ^{[1
]}

Gardner, E. E. ^{[1
]}

Sandborn, W. J. ^{[2
]}

Schmiegelow, K. ^{[3
,4
]}

Pui, C-H ^{[5
]}

Yee, S. W. ^{[6
]}

Stein, C. M. ^{[7
]}

Carrillo, M. ^{[8
]}

Evans, W. E. ^{[1
]}

Klein, T. E. ^{[8
]}

机构：

[1] St Jude Childrens Hosp, Dept Pharmaceut Sci, Memphis, TN 38105 USA

[2] Univ Calif San Diego, Div Gastroenterol, La Jolla, CA 92093 USA

[3] Univ Copenhagen, Inst Gynaecol Obstet & Paediat, Copenhagen, Denmark

[4] Rigshosp, Dept Paediat, DK-2100 Copenhagen, Denmark

[5] St Jude Childrens Hosp, Dept Oncol, Memphis, TN 38105 USA

[6] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA

[7] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA

[8] Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA

来源：

CLINICAL PHARMACOLOGY & THERAPEUTICS | 2011年 / 89卷 / 03期

关键词：

ACUTE LYMPHOBLASTIC-LEUKEMIA; S-METHYLTRANSFERASE; GENETIC-POLYMORPHISM; MERCAPTOPURINE METABOLISM; AZATHIOPRINE; THERAPY; TPMT; 6-MERCAPTOPURINE; DEFICIENCY; TOXICITY;

D O I：

10.1038/clpt.2010.320

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Thiopurine methyltransferase (TPMT) activity exhibits monogenic co-dominant inheritance, with ethnic differences in the frequency of occurrence of variant alleles. With conventional thiopurine doses, homozygous TPMT-deficient patients (similar to 1 in 178 to 1 in 3,736 individuals with two nonfunctional TPMT alleles) experience severe myelosuppression, 30-60% of individuals who are heterozygotes (similar to 3-14% of the population) show moderate toxicity, and homozygous wildtype individuals (similar to 86-97% of the population) show lower active thioguanine nucleolides and less myelosuppression. We provide dosing recommendations (updates at http://www.pharmgkb.org) for azathioprine, mercaptopurine ( MP), and thioguanine based on TPMT genotype.

引用

页码：387 / 391

页数：5

共 33 条

[1] Guidelines for prescribing azathioprine in dermatology [J].

Anstey, AV ;

Wakelin, S ;

Reynolds, NJ .

BRITISH JOURNAL OF DERMATOLOGY, 2004, 151 (06) :1123-1132

[2] The Seventh International Childhood Acute Lymphoblastic Leukemia Workshop Report: Palermo, Italy, January 29–30, 2005 [J].

M Aricó ;

A Baruchel ;

Y Bertrand ;

A Biondi ;

V Conter ;

T Eden ;

H Gadner ;

P Gaynon ;

K Horibe ;

S P Hunger ;

G Janka-Schaub ;

G Masera ;

J Nachman ;

R Pieters ;

M Schrappe ;

K Schmiegelow ;

M G Valsecchi ;

C-H Pui .

Leukemia, 2005, 19 (7) :1145-1152

[3] Thiopurine methyltransferase genotype predicts therapy-limiting severe toxicity from azathioprine [J].

Black, AJ ;

McLeod, HL ;

Capell, HA ;

Powrie, RH ;

Matowe, LK ;

Pritchard, SC ;

Collie-Duguid, ESR ;

Reid, DM .

ANNALS OF INTERNAL MEDICINE, 1998, 129 (09) :716-718

[4] Variation in Care in Pediatric Crohn Disease [J].

Colletti, Richard B. ;

Baldassano, Robert N. ;

Milov, David E. ;

Margolis, Peter A. ;

Bousvaros, Athos ;

Crandall, Wallace V. ;

Crissinger, Karen D. ;

D'Amico, Michael A. ;

Day, Andrew S. ;

Denson, Lee A. ;

Dubinsky, Marla ;

Ebach, Dawn R. ;

Hoffenberg, Edward J. ;

Kader, Howard A. ;

Keljo, David J. ;

Leibowitz, Ian H. ;

Mamula, Petar ;

Pfefferkorn, Marian D. ;

Qureshi, M. Azim .

JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION, 2009, 49 (03) :297-303

[5] Preponderance of thiopurine S-methyltransferase deficiency and heterozygosity among patients intolerant to mercaptopurine or azathioprine [J].

Evans, WE ;

Hon, YY ;

Bomgaars, L ;

Coutre, S ;

Holdsworth, M ;

Janco, R ;

Kalwinsky, D ;

Keller, F ;

Khatib, Z ;

Margolin, J ;

Murray, J ;

Quinn, J ;

Ravindranath, Y ;

Ritchey, K ;

Roberts, W ;

Rogers, ZR ;

Schiff, D ;

Steuber, C ;

Tucci, F ;

Kornegay, N ;

Krynetski, EY ;

Relling, MV .

JOURNAL OF CLINICAL ONCOLOGY, 2001, 19 (08) :2293-2301

[6] Pharmacogenetics of thiopurine S-Methyltransferase and thiopurine therapy [J].

Evans, WE .

THERAPEUTIC DRUG MONITORING, 2004, 26 (02) :186-191

[7] 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

[8] Current use of pharmacogenetic testing: a national survey of thiopurine methyltransferase testing prior to azathioprine prescription [J].

Fargher, E. A. ;

Tricker, K. ;

Newman, W. ;

Elliott, R. ;

Roberts, S. A. ;

Shaffer, J. L. ;

Bruce, I. ;

Payne, K. .

JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS, 2007, 32 (02) :187-195

[9] Thiopurine S-methyltransferase (TPMT) assessment prior to starting thiopurine drug treatment; a pharmacogenomic test whose time has come [J].

Ford, L. T. ;

Berg, J. D. .

JOURNAL OF CLINICAL PATHOLOGY, 2010, 63 (04) :288-295

[10] Improving pharmacovigilance in Europe: TPMT genotyping and phenotyping in the UK and Spain [J].

Gurwitz, David ;

Rodriguez-Antona, Cristina ;

Payne, Katherine ;

Newman, William ;

Gisbert, Javier P. ;

Gutierrez de Mesa, Emma ;

Ibarreta, Dolores .

EUROPEAN JOURNAL OF HUMAN GENETICS, 2009, 17 (08) :991-998

← 1 2 3 4 →