• 1
    Lennard L. The clinical pharmacology of 6-mercaptopurine. Eur. J. Clin. Pharmacol. 1992; 43: 32939.
  • 2
    Elion GB. The George Hitchings and Gertrude Elion Lecture. The pharmacology of azathioprine. Ann. NY Acad. Sci. 1993; 685: 4007.
  • 3
    Mason M, Currey HL, Barnes CG, Dunne JF, Hazleman BL, Strickland ID. Azathioprine in rheumatoid arthritis. BMJ 1969; 1: 4202.
  • 4
    Brooke BN, Hoffmann DC, Swarbrick ET. Azathioprine for Crohn's disease. Lancet 1969; 2: 61214.
  • 5
    Rhodes J, Bainton D, Beck P. Azathioprine in Crohn's disease. Lancet 1970; 2: 1142.
  • 6
    Markowitz J, Grancher K, Kohn N, Lesser M, Daum F. A multicenter trial of 6-mercaptopurine and prednisone in children with newly diagnosed Crohn's disease. Gastroenterology 2000; 119: 895902.
  • 7
    Sandborn W, Sutherland L, Pearson D, May G, Modigliani R, Prantera C. Azathioprine or 6-mercaptopurine for inducing remission of Crohn's disease. Cochrane Database Syst. Rev. 2000; CD000545.
  • 8
    Pearson DC, May GR, Fick G, Sutherland LR. Azathioprine for maintaining remission of Crohn's disease. Cochrane Database Syst. Rev. 2000; CD000067.
  • 9
    Gearry R, Barclay M, Burt M, Collett J, Chapman B. Thiopurine drug adverse effects in a population of New Zealand patients with inflammatory bowel disease. Pharmacoepidemiol. Drug Saf. 2004; 13: 5637.
  • 10
    Fraser AG, Orchard TR, Jewell DP. The efficacy of azathioprine for the treatment of inflammatory bowel disease: a 30 year review. Gut 2002; 50: 4859.
  • 11
    Weinshilboum RM, Sladek SL. Mercaptopurine pharmacogenetics: monogenic inheritance of erythrocyte thiopurine methyltransferase activity. Am. J. Hum. Genet. 1980; 32: 65162.
  • 12
    Ameyaw MM, Collie-Duguid ES, Powrie RH, Ofori-Adjei D, McLeod HL. Thiopurine methyltransferase alleles in British and Ghanaian populations. Hum. Mol. Genet. 1999; 8: 36770.
  • 13
    McLeod HL, Pritchard SC, Githang’a J et al. Ethnic differences in thiopurine methyltransferase pharmacogenetics: evidence for allele specificity in Caucasian and Kenyan individuals. Pharmacogenetics 1999; 9: 7736.
  • 14
    Gearry RB, Barclay ML, Burt MJ et al. Thiopurine S-methyltransferase (TPMT) genotype does not predict adverse drug reactions to thiopurine drugs in patients with inflammatory bowel disease. Aliment. Pharmacol. Ther. 2003; 18: 395400.
  • 15
    Haglund S, Lindqvist M, Almer S, Peterson C, Taipalensuu J. Pyrosequencing of TPMT alleles in a general Swedish population and in patients with inflammatory bowel disease. Clin. Chem. 2004; 50: 28895.
  • 16
    Larovere LE, De Kremer RD, Lambooy LH, De Abreu RA. Genetic polymorphism of thiopurine S-methyltransferase in Argentina. Ann. Clin. Biochem. 2003; 40: 38893.
  • 17
    Isaza C, Henao J, Lopez AM, Cacabelos R. Allelic variants of the thiopurine methyltransferase (TPMT) gene in the Colombian population. Methods Find. Exp. Clin. Pharmacol. 2003; 25: 4239.
  • 18
    Hon YY, Fessing MY, Pui CH, Relling MV, Krynetski EY, Evans WE. Polymorphism of the thiopurine S-methyltransferase gene in African–Americans. Hum. Mol. Genet. 1999; 8: 3716.
  • 19
    Loennechen T, Utsi E, Hartz I, Lysaa R, Kildalsen H, Aarbakke J. Detection of one single mutation predicts thiopurine S-methyltransferase activity in a population of Saami in northern Norway. Clin. Pharmacol. Ther. 2001; 70: 1838.
  • 20
    Collie-Duguid ES, Pritchard SC, Powrie RH et al. The frequency and distribution of thiopurine methyltransferase alleles in Caucasian and Asian populations. Pharmacogenetics 1999; 9: 3742.
  • 21
    Kham SK, Tan PL, Tay AH, Heng CK, Yeoh AE, Quah TC. Thiopurine methyltransferase polymorphisms in a multiracial asian population and children with acute lymphoblastic leukemia. J. Pediatr. Hematol. Oncol. 2002; 24: 3539.
  • 22
    Hamdy SI, Hiratsuka M, Narahara K et al. Genotype and allele frequencies of TPMT, NAT2, GST, SULT1A1 and MDR-1 in the Egyptian population. Br. J. Clin. Pharmacol. 2003; 55: 5609.
  • 23
    Kumagai K, Hiyama K, Ishioka S et al. Allelotype frequency of the thiopurine methyltransferase (TPMT) gene in Japanese. Pharmacogenetics 2001; 11: 2758.
  • 24
    Chang JG, Lee LS, Chen CM et al. Molecular analysis of thiopurine S-methyltransferase alleles in South-east Asian populations. Pharmacogenetics 2002; 12: 1915.
  • 25
    Reuther LO, Sonne J, Larsen N, Dahlerup JF, Thomsen OO, Schmiegelow K. Thiopurine methyltransferase genotype distribution in patients with Crohn's disease. Aliment. Pharmacol. Ther. 2003; 17: 658.
  • 26
    Roberts RL, Barclay ML, Gearry RB, Kennedy MA. A multiplexed allele-specific polymerase chain reaction assay for the detection of common thiopurine S-methyltransferase (TPMT) mutations. Clin. Chim. Acta 2004; 341: 4953.
  • 27
    Spire-Vayron de la Moureyre C, Debuysere H, Mastain B et al. Genotypic and phenotypic analysis of the polymorphic thiopurine S-methyltransferase gene (TPMT) in a European population. Br. J. Pharmacol. 1998; 125: 87987.
  • 28
    Evans WE, Hon YY, Bomgaars L et al. Preponderance of thiopurine S-methyltransferase deficiency and heterozygosity among patients intolerant to mercaptopurine or azathioprine. J. Clin. Oncol. 2001; 19: 2293301.
  • 29
    Coulthard SA, Howell C, Robson J, Hall AG. The relationship between thiopurine methyltransferase activity and genotype in blasts from patients with acute leukemia. Blood 1998; 92: 285662.
  • 30
    Schwab M, Schaeffeler E, Marx C, Zanger U, Aulitzky W, Eichelbaum M. Shortcoming in the diagnosis of TPMT deficiency in a patient with Crohn's disease using phenotyping only. Gastroenterology 2001; 121: 4989.
  • 31
    Weyer N, Kroplin T, Fricke L, Iven H. Human thiopurine S-methyltransferase activity in uremia and after renal transplantation. Eur. J. Clin. Pharmacol. 2001; 57: 12936.
  • 32
    Lysaa RA, Giverhaug T, Wold HL, Aarbakke J. Inhibition of human thiopurine methyltransferase by furosemide, bendroflumethiazide and trichlormethiazide. Eur. J. Clin. Pharmacol. 1996; 49: 3936.
  • 33
    Lowry PW, Franklin CL, Weaver AL et al. Leucopenia resulting from a drug interaction between azathioprine or 6-mercaptopurine and mesalamine, sulphasalazine, or balsalazide. Gut 2001; 49: 65664.
  • 34
    Dubinsky MC, Yang H, Hassard PV et al. 6-MP metabolite profiles provide a biochemical explanation for 6-MP resistance in patients with inflammatory bowel disease. Gastroenterology 2002; 122: 90415.
  • 35
    Kaskas BA, Louis E, Hindorf U et al. Safe treatment of thiopurine S-methyltransferase deficient Crohn's disease patients with azathioprine. Gut 2003; 52: 1402.
  • 36
    Seidman EG. Clinical use and practical application of TPMT enzyme and 6-mercaptopurine metabolite monitoring in IBD. Rev. Gastroenterol. Disord. 2003; 3 (Suppl. 1): S308.
  • 37
    Dubinsky MC. Optimizing immunomodulator therapy for inflammatory bowel disease. Curr. Gastroenterol. Rep. 2003; 5: 50611.
  • 38
    Colombel JF, Ferrari N, Debuysere H et al. Genotypic analysis of thiopurine S-methyltransferase in patients with Crohn's disease and severe myelosuppression during azathioprine therapy. Gastroenterology 2000; 118: 102530.
  • 39
    Black AJ, McLeod HL, Capell HA et al. Thiopurine methyltransferase genotype predicts therapy-limiting severe toxicity from azathioprine. Ann. Intern. Med. 1998; 129: 71618.
  • 40
    Tavadia SM, Mydlarski PR, Reis MD et al. Screening for azathioprine toxicity: a pharmacoeconomic analysis based on a target case. J. Am. Acad. Dermatol. 2000; 42: 62832.
  • 41
    Schwab M, Schaffeler E, Marx C et al. Azathioprine therapy and adverse drug reactions in patients with inflammatory bowel disease: impact of thiopurine S-methyltransferase polymorphism. Pharmacogenetics 2002; 12: 42936.
  • 42
    Marinaki A, Ansari A, Duley J et al. Adverse drug reactions to azathioprine therapy are associated with polymorphism in the gene encoding inosine triphosphate pyrophosphatase (ITPase). Pharmacogenetics 2004; 14: 1817.
  • 43
    Aberra FN, Lewis JD, Hass D, Rombeau JL, Osborne B, Lichtenstein GR. Corticosteroids and immunomodulators: postoperative infectious complication risk in inflammatory bowel disease patients. Gastroenterology 2003; 125: 3207.
  • 44
    Lowry PW, Franklin CL, Weaver AL et al. Measurement of thiopurine methyltransferase activity and azathioprine metabolites in patients with inflammatory bowel disease. Gut 2001; 49: 66570.
  • 45
    Campbell S, Kingstone K, Ghosh S. Relevance of thiopurine methyltransferase activity in inflammatory bowel disease patients maintained on low-dose azathioprine. Aliment. Pharmacol. Ther. 2002; 16: 38998.
  • 46
    Reuther LO, Sonne J, Larsen NE et al. Pharmacological monitoring of azathioprine therapy. Scand. J. Gastroenterol. 2003; 38: 9727.
  • 47
    Evans WE. Thiopurine S-methyltransferase: a genetic polymorphism that affects a small number of drugs in a big way. Pharmacogenetics 2002; 12: 4213.
  • 48
    Gearry RB, Roberts RL, Barclay ML, Kennedy MA. Lack of association between the ITPA 94C > A polymorphism and adverse side effects from azathioprine. Pharmacogenetics 2004; 14: 77981.
  • 49
    Allorge D, Hamdan R, Broly F, Libersa C, Colombel JF. ITPA genotyping text does not improve detection of Crohn's disease patients at risk of azathioprine/6-mercaptopurine induced myelosuppresion. Gut 2005; 54: 565.
  • 50
    Lennard L. TPMT in the treatment of Crohn's disease with azathioprine. Gut 2002; 51: 1436.
  • 51
    Vogt MH, Stet EH, De Abreu RA, Bokkerink JP, Lambooy LH, Trijbels FJ. The importance of methylthio-IMP for methylmercaptopurine ribonucleoside (Me-MPR) cytotoxicity in Molt F4 human malignant T-lymphoblasts. Biochim. Biophys. Acta 1993; 1181: 18994.
  • 52
    Tiede I, Fritz G, Strand S et al. CD28-dependent Rac1 activation is the molecular target of azathioprine in primary human CD4+ T lymphocytes. J. Clin. Invest. 2003; 111: 113345.
  • 53
    Paerregaard A, Schmiegelow K. Monitoring azathioprine metabolite levels and thiopurine methyl transferase (TPMT) activity in children with inflammatory bowel disease. Scand. J. Gastroenterol. 2002; 37: 3712.
  • 54
    Belaiche J, Desager JP, Horsmans Y, Louis E. Therapeutic drug monitoring of azathioprine and 6-mercaptopurine metabolites in Crohn disease. Scand. J. Gastroenterol. 2001; 36: 716.
  • 55
    Cuffari C, Theoret Y, Latour S, Seidman G. 6-Mercaptopurine metabolism in Crohn's disease: correlation with efficacy and toxicity. Gut 1996; 39: 4016.
  • 56
    Cuffari C, Hunt S, Bayless T. Utilisation of erythrocyte 6-thioguanine metabolite levels to optimise azathioprine therapy in patients with inflammatory bowel disease. Gut 2001; 48: 6426.
  • 57
    Dubinsky MC, Lamothe S, Yang HY et al. Pharmacogenomics and metabolite measurement for 6-mercaptopurine therapy in inflammatory bowel disease. Gastroenterology 2000; 118: 70513.
  • 58
    Dubinsky MC, Feldman EJ, Abreu MT, Targan SR, Vasiliauskas EA. Thioguanine: a potential alternate thiopurine for IBD patients allergic to 6-mercaptopurine or azathioprine. Am. J. Gastroenterol. 2003; 98: 105863.
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  • 59
    Dubinsky M, Vasiliauskas EDD, Singh HDD et al. 6-thioguanine can cause serious liver injury in inflammatory bowel disease patients. Gastroenterology 2003; 125: 298303.
  • 60
    Wright S, Sanders DS, Lobo AJ, Lennard L. Clinical significance of azathioprine active metabolite concentrations in inflammatory bowel disease. Gut 2004; 53: 11238.