TY - JOUR
T1 - Comparison of repeated-dose pharmacokinetics of prolonged-release and immediate-release torasemide formulations in healthy young volunteers
AU - Barbanoj, M. J.
AU - Ballester, M. R.
AU - Antonijoan, R. M.
AU - Gich, I.
AU - Pelagio, P.
AU - Gropper, S.
AU - Santos, B.
AU - Guglietta, A.
PY - 2009/2/1
Y1 - 2009/2/1
N2 - 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.
AB - 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.
KW - Bioavailability/absorption
KW - Healthy volunteers
KW - Pharmacokinetics
KW - Prolonged-release formulation
KW - Repeated-dose
KW - Torasemide
U2 - 10.1111/j.1472-8206.2008.00643.x
DO - 10.1111/j.1472-8206.2008.00643.x
M3 - Article
SN - 0767-3981
VL - 23
SP - 115
EP - 125
JO - Fundamental and Clinical Pharmacology
JF - Fundamental and Clinical Pharmacology
IS - 1
ER -