HIGH-DOSE TORASEMIDE, GIVEN ONCE-DAILY INTRAVENOUSLY FOR ONE WEEK, INPATIENTS WITH ADVANCED CHRONIC-RENAL-FAILURE

Effects, both acute and after repeated dosing of 200 mg of intravenous torasemide in comparison to baseline values on placebo, were investig ated with respect to 24 h fractional volume excretion and electrolyte excretion, signs of peripheral edema and changes in body weight in the present open uncontrolled multicenter study. Fourty-four patients wit h advanced chronic renal failure (mean creatinine clearance 8.9 +/- 9. 6 ml/min, range 1.1-63.7 ml/min) were enrolled after they had given th eir informed consent. The increase vs placebo in the primary efficacy variable 24 h fractional volume excretion was statistically significan t both acutely (p = 0.0001) and after repeated daily injections (p = 0 .0012). The acute changes of the means of fractional volume excretion (from 14.32% to 21.07%) and of absolute 24 h urinary volume (from 1303 mi to 2124 mi) were as expected from earlier data. In addition to the acute results our study showed that after seven days of daily injecti ons there was still a considerable diuretic effect (mean fractional vo lume excretion: 18.10%, absolute 24 h urinary volume: 1664 mi). Our da ta support earlier results in that the change in fractional potassium excretion was considerably smaller than that of sodium and chloride ex cretion. However, this effect which was more pronounced after acute ad ministration of torasemide seems to vanish after repeated dosing. Afte r repeated dosing there was only a minor change in calcium excretion a nd there was no alteration in phosphate excretion, neither acutely nor with repeated dosing. Along with the enhanced diuresis there was a re levant reduction in body weight and a clinical significant improvement in preexisting signs of peripheral edema. Torasemide was found to be also efficacious in patients on hemodialysis (with residual diuresis o f greater than or equal to 300 mi): after the first i.v. dose of 200 m g torasemide the mean fractional volume excretion was increased from 1 6.22% at baseline by 3.42% to 18.99% (in absolute 24 h urinary volume from 1014 mi at baseline by 563 mi to 1607 mi). In parallel, the mean fractional sodium excretion was inceased from 8.67% at baseline by 2.9 9% to 11.14% (in absolute 24 h urinary sodium excretion from 83.8 mmol at baseline by 51.2 mmol to 128.0 mmol). There were no serious advers e events related to the administration of torasemide. Torasemide appea rs to be a good choice for the treatment of patients with renal failur e.