PHARMACOKINETICS AND PHARMACODYNAMICS OF TORASEMIDE AND FUROSEMIDE INPATIENTS WITH DIURETIC RESISTANT ASCITES

Background/Aim: To evaluate the pharmacokinetics and pharmacodynamics of furosemide and torasemide in patients with cirrhosis and diuretic r esistant ascites. Methods: Eighteen patients were randomly allocated t o receive intravenous torasemide (40 mg) or furosemide (80 mg). The re nal response to these drugs was assessed in baseline conditions and in the 24 h following drug administration together with plasma and urina ry concentrations of furosemide, torasemide and its metabolites. Resul ts: Torasemide induced significantly greater diuretic and natriuretic effects than furosemide in the first hour after drug administration. N o other significant differences between the two drugs were observed wi th respect to the renal response to these drugs. Torasemide reached a lower maximum plasma concentration than furosemide, but the former dru g had a longer apparent terminal half-life and lower renal and non-ren al clearances. Comparing these results with those previously reported in healthy subjects, both drugs showed a reduced elimination rate thro ugh renal and non-renal routes, and a larger distribution to body flui ds. As a consequence, the half-life of both drugs was longer than in h ealthy subjects. Urinary excretion of pharmacologically active species , however, was quantitatively unchanged after torasemide administratio n, whereas it was reduced after furosemide. Finally, the natriuretic p otency of both drugs was markedly reduced in these patients. Conclusio ns: The pharmacokinetics and pharmacodynamics of torasemide and furose mide are markedly altered in patients with diuretic resistant ascites.