Inhibition of human thiopurine methyltransferase by furosemide, bendroflumethiazide and trichlormethiazide.

Article Details

Citation

Lysaa RA, Giverhaug T, Wold HL, Aarbakke J

Inhibition of human thiopurine methyltransferase by furosemide, bendroflumethiazide and trichlormethiazide.

Eur J Clin Pharmacol. 1996;49(5):393-6.

PubMed ID
8866635 [ View in PubMed
]
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 microM, 360 microM 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.

DrugBank Data that Cites this Article

Drug Enzymes
DrugEnzymeKindOrganismPharmacological ActionActions
BendroflumethiazideThiopurine S-methyltransferaseProteinHumans
Unknown
Inhibitor
Details
TrichlormethiazideThiopurine S-methyltransferaseProteinHumans
Unknown
Inhibitor
Details