Our pharmacokinetic studies with 95 healthy subjects, treated with torasemide showed after 3 to 4h a significant reduction of the fractional excretion (FE) of urate. Torasemide is currently the most efficient loop diuretic. It is metabolized in the liver to five different compounds. After active renal secretion torasemide inhibits reabsorption of sodium and chloride. It is not clear, which transport systems mediate the secretion of torasemide and its main metabolites M1, M3 and M5, and what is the reason for the reduction of FE of urate. In the present study, we demonstrate the interaction of torasemide and its metabolites M1, M3 and M5 with hOAT1, hOAT3 and hOAT4. [3H]p-aminohippurate (PAH) uptake by hOAT1, and [3H]estrone sulfate (ES) uptake by hOAT3 and hOAT4 were significantly inhibited. The affinity of each transporter to torasemide and its metabolites was determined by Dixon-plots, revealing Ki values of 55.1, 124.6, 145.5 and 75.4 mM for hOAT1 for torasemide, M1, M3, and M5, respectively. hOAT3 exhibited similar affinities for torasemide, M1, M3 (89 mM), whereas the Ki value for M5 was 59.5 mM. hOAT4 showed the highest affinity for torasemide, M3 and M1 with 45.0 mM 54.7mM and 107.2 mM, respectively. OAT4 did not show any interaction with M5. The reason for reduction of FE of urate are an inhibition of hOAT3-mediated urate secretion or/and a stimulation of urate reabsorption mediated by hOAT4.