Effects of five drugs including ciclosporin and nifedipine which were usually used in patients with kidney transplantation on erythrocyte thiopurinemethyltransferase activity

Abstract

Abstract: AIM: To investigate the effects of five dugs which were usually used simultaneously with azathioprine (AZA) in patients with kidney transplantation: ciclosporin, hydrocortisone, nifedipine, captopriland al-lopurinol on erythrocyte tliopuriner methyltransferase(TPMT) activity. METHODS: The erythrocyte TPMT activity of healthy volunteers was measured by high-per-formance liquid chromatography (HPLC). Sixteen volunteers were chosen, in which 8 cases with intermediate TPMT activity and others with normal TPMT activity. Themean inhibition ratio of each drug concentration and the mean IC values of the inhibitors were determined. RESULTS: Ciclosporin, hydrocortisone, captopril and allo-purinol had nearly no impacts on TPMT activity. Nifedip-lnehighly inhibited TPMT activity in vitro, the meanI IC₅₀ value in intermediate TPMT activity groupwas (24±17) μg/mL and in normal TPMT activity group was (12±10) μg/mL. CONCLUSION: The co-administration of nifedipine and thiopurines may lead to drug interactions.

Key words: thiopurine methyltransferase, azathio-prine, ciclosporin, hydrocortisone, nifedipine, captopril, allopurinol

CLC Number:

R969

XIONG Hui, XIONG Lei, SU Dan, XIN Hua-wen, WU Xiao-chun, LI Qing, LI Gao. Effects of five drugs including ciclosporin and nifedipine which were usually used in patients with kidney transplantation on erythrocyte thiopurinemethyltransferase activity[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2007, 12(12): 1411-1414.

References

[1] Lennard L. TPMT in the treatment of Crohn's disease with aza-thioprine[J]. Gut, 2002:51:143-146.
[2] Schaffeler E, Fischer C. Brockmeier D.et al. Comprehensive analysis of thiopurine S-methyltransferase phenotype: genotypecorrelation in al large population of German-Caucasians and iden-tifcation of tnovel TPMT variants[J]. Pharmacogenetics, 2004;14:407-417.
[3] Lysau RA, Giverhaug T, Wold HL, et al.Inhibition of human thiopurine Smelhylransferase by furosermide, bendroflumethe-iazide and trichlormethiazide[J]. Eur J Chin Pharmacol, 1996;49:393-396.
[4] 宰华雯,Fischer C, Schwab M,等.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; 10:655-658.
[5] Fgan LJ. Drug interactions in gastroenterology: mechanisms, consequences, and how to avoid[J]. Clin Gastroenterol Hepa-tol, 2004;2:725-730.
[6] Xin H,Fischer C, Schwab M, et al. Effects of aninosalicylates on thiopurine S-methyltransferase activity: an ex vivo study inpatients with inflammatory bowel disease[J]. Aliment Phamacol Ther, 2005;21:1105-1109.
[7] 熊晖,熊磊,苏丹,等,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: 738-740.
[8] Jacqz-Aigrain E, Bessa E, Medard Y, et al. Thiopurine meth-yltransferase activity in a French population: h. p.l.c. assayconditions and effects of drugs and inhibitors[J]. Br J Clin Phar-macol, 1994;38:1-8.
[9] Holme SA, Duley JA, Sanderson J, et al. Erythrecyte thiopurine methyltransferase assessmentprior to Azathiopurine use in the UK[J]. QJM, 2002;95:439-444.
[10] Cara CJ, Pena AS, Sans M.et al.Reviewing the mechanism of actionof thiopurine drugs: Towards a new paradign in clinical practice[J]. Med Sci Monit, 2004;10:247-254.
[11] Oselin K, Anier K. Inhibition of Human Thiopurine S Methyl-transfenase by Various Nonsteroidal Anti-inflammatory Drugs inVito: A Mechanism for Possible Drug interactions[J]. DrugMetab Dispos, 2007;35: 1452-1454.
[12] Chien SC, Uang YS, Lin HY, et al.Pharmacokinetics of nife-dipine in Taiwanese [J]. Biopharm Drug Dispos, 2004;25:77-84.
[13] Niopas l, Daftsios AC. Detemination of nifedipine in human plasma by solid-phase extraction and high-performance liquid chromatography: validation and application to pharmacokinetic studies[J]. J Pharn Biomed Anal, 2003; 32:1213-1218.

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