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Comparison of repeated‐dose pharmacokinetics of prolonged‐release and immediate‐release torasemide formulations in healthy young volunteers
Author(s) -
Barbanoj M.J.,
Ballester M.R.,
Antonijoan R.M.,
Gich I.,
Pelagio P.,
Gropper S.,
Santos B.,
Guglietta A.
Publication year - 2009
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.2008.00643.x
Subject(s) - tolerability , pharmacokinetics , medicine , urine , bioequivalence , diuretic , adverse effect , anesthesia , urology , pharmacology
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.