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

中国临床药理学与治疗学 ›› 2005, Vol. 10 ›› Issue (6): 655-658.

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

辛华雯, Christine Fischer, Matthias Schwab, Ulrich Klotz

广州军区武汉总医院临床药理科, 武汉430070, 湖北; ¹Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart 70376, Germany

收稿日期:2005-03-21 修回日期:2005-05-08 出版日期:2005-06-26 发布日期:2020-11-12
通讯作者: 辛华雯, 女, 医学博士, 副主任医师, 主要从事临床药理学研究。Tel:027-68878689 E-mail: huawenxin2005@hotmail.com

Effects of furosemide, piretanide and azathioprine on thiopurine methyltransferase activity in red blood cells from patients with chronic inflammatory bowel disease

XIN Hua-wen, FISCHER Christine¹, SCHWAB Matthias¹, KLOTZ Ulrich¹

Department of Clinical Pharmacology, Wuhan General Hospital, Wuhan 430070, Hubei, China; ¹Dr. Margarete Fischer-Bosch, Institute of Clinical Pharmacology, Stuttgart 70376, Germany

Received:2005-03-21 Revised:2005-05-08 Online:2005-06-26 Published:2020-11-12

摘要/Abstract

摘要： 目的: 研究利尿剂速尿、苯氧比酸及其硫唑嘌呤对慢性炎症性肠病患者红细胞硫嘌呤甲基转移酶(TPMT) 活性的影响。方法: 应用高效液相法(HPLC) 测定慢性炎症性肠病患者红细胞TPMT 活性, 其中中等活性、正常活性、较高活性的患者各6例, 依据浓度效应曲线计算每个药物的IC₅₀。结果: 速尿对TPMT 活性的抑制作用较强, 平均IC₅₀ 为15~19 μmol·L^-1, 在健康志愿者的正常血浆浓度范围内。苯氧比酸和硫唑嘌呤的平均IC₅₀ 值分别为300~ 313 μmol·L^-1 、430 ~ 532 μmol·L^-1, 均远高于体内所能达到的血浆浓度。3 种药物的IC₅₀值在3 个不同TPMT 活性组间无明显差异(P >0.05) 。结论: 速尿可抑制红细胞TPMT 活性, 当速尿和硫嘌呤类药物合用时, 应警惕发生不良相互作用。

关键词: 硫嘌呤甲基转移酶, 速尿, 苯氧比酸, 硫唑嘌呤, 炎症性肠病

Abstract: AIM: To study the possible effects of furosemide, piretanide and azathioprine on thiopurine methyltransferase (TPMT) activity in red blood cells (RBC) from patients with chronic inflammatory bowel disease (IBD). METHODS: The inhibitory potential of furosemide, piretanide and azathioprine on TPMT activity in RBC was assessed in vitro by HPLC in three groups of patients with very high, normal and intermediate TPMT activity (n =6 in each). Individual concentration response curves IC₅₀-values were determined. RESULTS: Independent of the basal TPMT activity, lowest IC₅₀-values were calculated for furosemide (15-19 μmol·L^-1), followed by piretanide (300-313 μmol·L^-1) and azathioprine (430-532 μmol·L^-1). Compared with reported plasma concentration achieved during treatment, only furosemide showed the potential to inhibit TPMT in vivo, whereas the IC₅₀-values of the other agents were far above the corresponding plasma levels. CONCLUSION: Only furosemide has the potential to inhibit TPMT activity in patients with IBD. Clinically relevant drug interactions should be considered in patients treated simultaneously with this diuretic and thiopurines.

Key words: TPMT, furosemide, piretanide, azathioprine, chronic inflammatory bowel disease

中图分类号:

R983.1

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.

XIN Hua-wen, FISCHER Christine, SCHWAB Matthias, KLOTZ Ulrich. Effects of furosemide, piretanide and azathioprine on thiopurine methyltransferase activity in red blood cells from patients with chronic inflammatory bowel disease[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2005, 10(6): 655-658.

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