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

Abstract

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

CLC Number:

R983.1

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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