1996
DOI: 10.1007/s002280050038
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Inhibition of human thiopurine methyltransferase by furosemide, bendroflumethiazide and trichlormethiazide

Abstract: 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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Cited by 45 publications
(31 citation statements)
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“…Finally, genotyping can reliably detect the major and rare variant at the human TPMT locus and may provide an explanation for TPMT deficiency [150]. Determination of the 3 most common alleles in Caucasians (*2, *3A, and *3C) identifies 90% to 96.2% of patients with altered enzyme activity [44,56,149] and may predict most AZA-induced toxicity.…”
Section: Genotyping Tpmt Vs Phenotyping Tpmtmentioning
confidence: 99%
“…Finally, genotyping can reliably detect the major and rare variant at the human TPMT locus and may provide an explanation for TPMT deficiency [150]. Determination of the 3 most common alleles in Caucasians (*2, *3A, and *3C) identifies 90% to 96.2% of patients with altered enzyme activity [44,56,149] and may predict most AZA-induced toxicity.…”
Section: Genotyping Tpmt Vs Phenotyping Tpmtmentioning
confidence: 99%
“…While leukopenia has been demonstated, 230 the severity of the interaction between these benzoic acid derivatives and azathioprine is not as well established as allopurinol. Furosemide has been shown in vivo to inhibit TPMT activity, 233 but its clinical relevance remains unknown. The prolonged use of trimethoprim-sulfamethoxazole in renal transplantation patients on azathioprine has been reported to cause neutropenia and thrombocytopenia.…”
Section: Drug Interactionsmentioning
confidence: 99%
“…65,78 In the patients receiving both thiopurines and mesalamine, adverse effects were observed more frequently. 78,79 TPMT activity may be inhibited also by therapeutic plasma levels of furosemide, thiazide diuretics, sulfasalazine, 5-acetylsalicylic acid, and nonsteroid antiinflammatory 67,80 Conversely, thiopurine therapy alone may increase activity of TPMT. 8,65,73 In some cases, monitoring of therapeutic 6-TGN blood concentrations may be as important as TPMT genotyping or phenotyping.…”
Section: Tpmt Polymorphismsmentioning
confidence: 94%