PHARMACOKINETICS OF TORASEMIDE AND ITS METABOLITES IN END-STAGE RENAL-DISEASE

The pharmacokinetics of torasemide. a new loop diuretic, as well as it s active metabolites M1 and M3, and its inactive main metabolite, M5, were studied in 12 patients with end-stage renal failure during single i.v. (n = 6) or single oral (n = 6) dosing of 200 mg torasemide, and during chronic oral treatment for 9 days (n = 12). The elimination hal f-life (t(1/2)) of torasemide was unchanged in renal failure, whereas t(1/2) of the torasemide metabolites M1, M3, and M5 were markedly prol onged. However t(1/2) as well as the area under the plasma level time curve ofplasma level time curve of torasemide and its metabolites were unchanged during chronic compared to acute administration. The result s of this study suggest that despite the increased half-life of torase mide metabolites M1, M3 and M5 in end-stage renal failure patients, no accumulation of the parent drug torasemide and its metabolites during chronic dosing is demonstrable.