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肾移植受者红细胞ITPA活性与硫唑嘌呤不良反应关系的研究 被引量：2

The study on the association between erythrocyte ITPA activity and azathioprine-related adverse drug reactions in renal transplant recipients
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摘要 目的建立一种测定三磷酸肌苷焦磷酸酶(ITPA)活性的高效液相色谱法(HPLC),探讨ITPA活性与硫唑嘌呤(AZA)导致的不良反应的关系。方法应用新建立的高效液相色谱法测定110例肾移植患者红细胞ITPA活性,分析ITPA活性在发生了不良反应的患者与未发生不良反应的患者间的差异。结果110例患者红细胞ITPA活性范围为2.0～575.7U,平均为(373.4±148.3)U,ITPA活性在男性和女性患者间无差异(P>0.05)。将76例未发生不良反应的患者作为对照组,其平均ITPA活性为(391.1±140.5)U。10例发生了血液毒性和14例发生了肝脏毒性的患者平均ITPA活性与对照组患者比较无差异(P>0.05)。10例发生了胃肠紊乱的患者平均ITPA活性为(177.1±69.6)U,明显低于未发生不良反应的患者(P<0.05)。结论硫唑嘌呤所致的血液毒性和肝脏毒性与ITPA活性无明显相关性,硫唑嘌呤所致的胃肠紊乱与ITPA活性低下有关。ITPA活性测定对指导临床硫唑嘌呤的合理应用具有一定意义。 Aim To establish an HPLC for measuring inosine triphosphate pyrophosphatase （ITPA） activity and investigate the association between ITPA activity and azathioprinerelated adverse reaction. Methods By means of the newly established HPLC, erythrocyte ITPA activity of 110 renal transplant recipients was determined, and the differences were analyzed in ITPA activity between groups of cases with adverse drug reactions and those without adverse drug reactions. Results The erythrocyte ITPA activity range of 110 pa tients was from 2.0U to 575.7U, and the mean value was （373.4 ± 148.3）U. There was no distinct differ ence in the ITPA activity between male and female patients （P 〉 0.05）. The 76 cases without adverse reactions were taken as the control group, whose mean IT- PA activity was （391.1 ± 140. 5 ） U. The mean ITPAactivity of the 10 case with hematotoxicity and the 14 cases with hepatotoxicity was not distinctly different from that of the control group （P 〉 0. 05 ）. The average ITPA activity of 10 cases with gastrointestinal disorders was （ 177. 1 ± 69. 6） U, much lower than that of the cases without adverse reactions （ P 〈 0. 05 ）. Conclusion There was no clear association between ITPA ac- tivity and hematotoxicity or hepatotoxicity. AZA induced. The AZA induced gastrointestinal disorders are related to the low ITPA activity. ITPA activity determination is significant to guiding the reasonable application of the clinical AZA.
作者 熊晖 辛华雯 熊磊 吴笑春 李罄 李高
机构地区 广州军区武汉总医院临床药理科 华中科技大学同济医学院药学院
出处 《中国药理学通报》 CAS CSCD 北大核心 2008年第11期1496-1500,共5页 Chinese Pharmacological Bulletin
基金 全军科学技术研究“十一五”计划资助课题(No06MA131)
关键词 硫唑嘌呤 三磷酸肌苷焦磷酸酶活性 高效液相色谱法 不良反应 azathioprine inosine triphosphate pyrophosphatase （ITPA） activity HPLC adverse drug reactions
分类号 R331.122 [医药卫生—人体生理学] R345 [医药卫生—基础医学]
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参考文献19

  • 1Formea C M, Myers-Huentelman H, Wu R, et al. Thiopurine S- methyltransferase genotype predict azathioprine-induced myelotoxicity inkidney transplant recipients [ J ]. Am J Transplant, 2004,4 (11) :18t0-7.
  • 2吴珏珩,张建萍,姜文奇,黄民.硫嘌呤甲基转移酶多态性的研究进展及其临床意义[J].癌症,2001,20(12):1439-1441. 被引量：6
  • 3Schaeffeler E, Lang T, Zanger U M, et al. Highthroughtput genotyping of thiopurine S-methyltransferase by denaturing HPLC [ J]. Clin Chem,2001,47(3 ) :548 - 55.
  • 4Sumi S, Marinaki A M, Arenas M, et al. Genetic basis of inosine triphosphate pyrophosphohydrolase deficiency [ J ]. Hum Genet, 2002,111 (4-5) :360 - 7.
  • 5Holmes S L, Turner B M, Hirsehhorrl K. Human inosine tfiphosphatase : catalytic properties and population studies [ J ]. Clin Chim Acta, 1979,97 ( 2-3 ) : 143 - 53.
  • 6Lin S,McLennan A G,Ying K,et al. Cloning expression and characterization of a human inosine triphosphate pyrophosphatase encoded by the itpa gene [ J ]. J Biol Chem, 2001,276 ( 22 ) : 18695 - 701.
  • 7Sumi S, Ueta A, Maeda T, et al. A Japanese case with inosine triphosphate pyrophosphohydrolase deficiency attributable to an enzymatic defect in white blood cells [ J ]. J Inherit Metab Dis,2004,27(2) :277 -8.
  • 8Duley J A, Simmonds H A, Hopkinson D A, Levinsky R J. Inosine triphosphate pyrophosphohydrolase deficiency in a kindred with adenosine deaminase deficiency [ J ]. Clin Chim Acta, 1990, 188 (3) :243 -52.
  • 9Holmes S L, Turner B M, Hirschhom K. Human inosine triphosphatase:catalytic properties and population studies[ J ]. Clin Chim Acta, 1979,97 (2-3) : 143 - 53.
  • 10Vanderheiden B S. Purification and properties of human erythrocyte inosine triphosphate pyrophosphohydrolase [ J ]. J Cell Physiol, 1979,98(1) :41 -7.

二级参考文献16

  • 1辛华雯,Christine Fischer,Matthias Schwab,Ulrich Klotz.速尿、苯氧比酸、硫唑嘌呤对慢性炎症性肠病患者红细胞TPMT活性的影响[J].中国临床药理学与治疗学,2005,10(6):655-658. 被引量：3
  • 2熊晖,熊磊,苏丹,辛华雯,吴笑春,李罄,李高.HPLC法检测人红细胞中巯嘌呤甲基转移酶的活性[J].中国药师,2007,10(8):738-740. 被引量：4
  • 3Jang I J，Br J Clin Pharmacol，1996年，42卷，5期，638页
  • 4Mcleod H L，Blood，1995年，85卷，7期，1897页
  • 5Lennard L. TPMT in the treatment of Crohn's disease with azathioprine[J]. Gut, 2002;51 : 143 - 146.
  • 6Schaeffeler E, Fischer C, Brockmeier D, et al. Comprehensive analysisof thiopurine S-methyltransferase phenotype-genotype correlation in a large population of German-Caucasians and identification of novel TPMT variants[J]. Pharmacogenetics, 2004; 14:407-417.
  • 7Lysaa RA, Giverhaug T, Wold HL, et al. Inhibition of human thiopurine S-methyltransferase by furosemide, bendrotlumetheiazide and trichlormethiazide[J]. Eur J Chin Pharmacol, 1996; 49:393 - 396.
  • 8Egan LJ. Drug interactions in gastroenterology: mechanisms, consequences, and how to avoid[ J]. Clin Gastroenterol Hepatol, 2004;2:725-730.
  • 9Xin H, Fischer C, Schwab M, et al. Effects of aminosalicylates on thiopurine S-methyltransferase activity: an ex vivo study in patients with inflammatory bowel disease[J]. Aliment Pharmacol Ther, 2005 ; 21 : 1105 - 1109.
  • 10Jacqz-Aigrain E, Bessa E, Medard Y, et al. Thiopurine methyltransferase activity in a French population: h.p. l. c. assay conditions and effectsof drugs and inhibitors[J]. Br J Clin Pharmaeol, 1994;38:1 - 8.

共引文献6

同被引文献28

  • 1Shipkova M, Lorenz K, Oellerich M, et al. Measurement of erythrocyte inosine triphosphate pyrophosphohydrolase (ITPA) activity by HPLC and correlation of ITPA geno- type-phenotype in a caucasian population[J]. Clin Chem, 2006,52(2) : 140 - 147.
  • 2Mascheretti S, Schreiber S. Genetic testing in crohn disease: utility in individualizing patient management [J]. Am J Pharmacogenom, 2005,5(4) :213 - 222.
  • 3Gearry RB, Barclay ML. Azathioprine and 6-mercaptopurine pharmacogenetics and metabolite monitoring in inflammatory bowel disease[ J]. J Gastroenterol Hepatol, 2005, 20(8) :1149 - 1157.
  • 4Mcleod HL, Pritchard SC, Githang' a J, et al. Ethnic differences in thiopurine methyltransferase pharmacogenetics: evidence for allele specificity in Caucasian and Kenyan individuals[J]. Pharmcogenetics, 1999,9(6) :773 - 776.
  • 5Collie-Duguid ES, Pritchard SC, Powrie RH, et al. The frequency and distribution of thiopurine methyltransferase allele in Caucasian and Asian populations[J]. Pharmcogenetics, 1999,9(1) :37 -42.
  • 6Weinshilboum R. Thiopurine pharmacogenetics: clinical and molecular studies of thiopurine methyhransferase[J]. Drug Metab Dispos, 2001,29(4) :601 - 605.
  • 7Marinaki AM, Ansari A, Duley JA, et al. Adverse drug reactions to azathioprine therapy are associated with polymorphism in the gene encoding inosine triphosphate pyrophosphatase (ITPA) [ J ]. Phanrracogenetics, 2004, 14(3):181 - 187.
  • 8Marsh S, King CR, Ahluwalia R, el al. Distribution of 1TPA P32T alleles in multiple wodd populations [ J ]. J Hum Genet, 2004,49(10) :579 - 581.
  • 9Marsh S, King CR, Ahluwalia R, el al. Distribution of 1TPA P32T alleles in multiple wodd populations [ J ]. J Hum C, enet, 2004,49(10) :579 - 581.
  • 10Duley JA, Marinaki AM, Arenas M, et al. Do ITPA and TPMT genotypes predict the development of side effects to AZA[J]? Gut, 2006,55(7):1048.

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中国药理学通报
2008年 第11期

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