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Inhibition of human thiopurine methyltransferase by furosemide, bendroflumethiazide and trichlormethiazide

European Journal of Clinical Pharmacology volume 49, pages 393–396 (1996)Cite this article

Abstract

Results: Incubation in vitro of human recombinant and erythrocyte (RBC) thiopurine methyl transferase (TPMT) with furosemide, bendroflumethiazide and trichlormethiazide demonstrated inhibition of both enzyme preparations, with IC50 values of 170 μM, 360 μM and 1 mM, respectively. Kinetic studies revealed that the inhibition was mixed or non-competitive with regard both to the thiopurine substrate 6-mercaptopurine (6-MP) and the methyl donor S-adenosyl-L-methionine.

Conclusion: Since S-methylation is a major pathway in the metabolism of thiopurines, our data point to the possibility of a clinically significant diuretic-thiopurine interaction in patients treated simultaneously with these drugs.

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Affiliations

  1. Department of Pharmacology, Institute of Medical Biology, University of Tromsø, MH-bygget, N-9037, Tromsø, Norway

    R. A. Lysaa, T. Giverhaug, H. Libæk Wold & J. Aarbakke

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  1. R. A. Lysaa
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  2. T. Giverhaug
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  3. H. Libæk Wold
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  4. J. Aarbakke
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Lysaa, R.A., Giverhaug, T., Libæk Wold, H. et al. Inhibition of human thiopurine methyltransferase by furosemide, bendroflumethiazide and trichlormethiazide. Eur J Clin Pharmacol 49, 393–396 (1996). https://doi.org/10.1007/BF00203784

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  • DOI: https://doi.org/10.1007/BF00203784

Key words

  • Thiopurine methyltransferase
  • diuretics
  • furosemide
  • bendroflumethiazide
  • trichlormethiazide