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), Cmax ratio = 0.69 (90% CI 0.67-0.73); and on day 4, ratio = 1.02 (90% CI 0.98-1.05), Cmax ratio = 0.62 (90% CI 0.55-0.70). PR had longer tmax 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. © 2009 Société Française de Pharmacologie et de Thérapeutique.
Original language | English |
---|---|
Pages (from-to) | 115-125 |
Journal | Fundamental and Clinical Pharmacology |
Volume | 23 |
Issue number | 1 |
DOIs | |
Publication status | Published - 1 Feb 2009 |
Keywords
- Bioavailability/absorption
- Healthy volunteers
- Pharmacokinetics
- Prolonged-release formulation
- Repeated-dose
- Torasemide