Comparison of repeated-dose pharmacokinetics of prolonged-release and immediate-release torasemide formulations in healthy young volunteers

Fundam Clin Pharmacol. 2009 Feb;23(1):115-25. doi: 10.1111/j.1472-8206.2008.00643.x.

Abstract

The major aim of the study was to compare the pharmacokinetic profile of repeated-dose administration of a prolonged-release (PR) formulation of torasemide with that of an immediate-release (IR) dosage. Sixteen volunteers received one daily dose, on four consecutive days, of 10 mg of torasemide-PR or torasemide-IR in a single-blind, two-treatment, two-period, repeated-dose, cross-over, sequence-randomized clinical trial. Blood samples were collected at various time points on day 1 (single-dose) and on day 4 (repeated-dose) and torasemide concentrations were analysed by LC/MS/MS. Diuretic effect and urine electrolytes were measured. Urinary urgency was subjectively assessed by visual analogue scales. Safety and tolerability were also determined. Based on logged values, bioequivalence parameters, were: on day 1, ratio = 1.07 (90% CI 1.02-1.1), C(max) ratio = 0.69 (90% CI 0.67-0.73); and on day 4, ratio = 1.02 (90% CI 0.98-1.05), C(max) ratio = 0.62 (90% CI 0.55-0.70). PR had longer t(max) than IR and showed significantly lower fluctuations of plasma concentrations. Urine evaluations were similar with both formulations, although PR showed a lower urine volume in the first hours post-administration. Episodes of acute urinary urgency occurred later and were subjectively less intensive with PR. No significant adverse events were reported.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Area Under Curve
  • Chromatography, Liquid
  • Cross-Over Studies
  • Delayed-Action Preparations
  • Diuretics / administration & dosage
  • Diuretics / adverse effects
  • Diuretics / pharmacokinetics*
  • Drug Administration Schedule
  • Electrolytes / urine
  • Female
  • Humans
  • Male
  • Single-Blind Method
  • Sulfonamides / administration & dosage
  • Sulfonamides / adverse effects
  • Sulfonamides / pharmacokinetics*
  • Tandem Mass Spectrometry
  • Therapeutic Equivalency
  • Torsemide
  • Young Adult

Substances

  • Delayed-Action Preparations
  • Diuretics
  • Electrolytes
  • Sulfonamides
  • Torsemide