Pharmacokinetics and pharmacodynamics of torasemide in patients with chronic renal insufficiency-Preliminary evaluation

The pharmacokinetics and pharmacodynamics of torasemide were studied in 24 subjects with chronic renal insufficiency. The subjects were divided into two groups of patients, half having a creatinine clearance <30 ml/min and the other half having a creatinine clearance between 30 and 60 ml/min. Three different intravenous doses were studied in each patient group. Pharmacokinetic analysis revealed dose proportionality when relating area under the concentration curve to dose. There was a progressive decrease in renal clearance of torasemide with declining renal function. In contrast, there was no difference in serum elimination half-life among the patients. In addition, this half-life was not different from that observed in healthy young or elderly control subjects. In previous reports on patients with congestive heart failure and liver disease, serum half-life values were prolonged compared to that of control subjects, presumably due to decreased hepatic, nonrenal clearance of torasemide. Supportive of this hypothesis is the considerably increased area under the serum vs. concentration time curve in such patients. In summary, this study has shown that the serum half-life of torasemide would be unchanged in patients with renal disease. The ceiling dose for torasemide (i.e., the dose above which no further drug-induced natriuresis is obtained) has been preliminarily found to be a single 100-mg intravenous dose in patients with moderate renal insufficiency and a single 200-mg intravenous dose in patients with severe disease.