Comparison of repeated-dose pharmacokinetics of prolonged-release and immediate-release torasemide formulations in healthy young volunteers.
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.
Barbanoj
M J
MJ
Drug Research Centre (CIM), Research Institute of Santa Creu and Sant Pau Hospital, Department of Pharmacology and Therapeutics, Autonomous University of Barcelona (UAB), Barcelona, Spain. mbarbanoj@santpau.cat
Ballester
M R
MR
Antonijoan
R M
RM
Gich
I
I
Pelagio
P
P
Gropper
S
S
Santos
B
B
Guglietta
A
A
D000328:Adult; D019540:Area Under Curve; D002853:Chromatography, Liquid; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004232:Diuretics / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D004573:Electrolytes / Q000652:urine; D005260:Female; D006801:Humans; D008297:Male; D016037:Single-Blind Method; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D053719:Tandem Mass Spectrometry; D013810:Therapeutic Equivalency; D000077786:Torsemide; D055815:Young Adult
D003692:Delayed-Action Preparations; D004232:Diuretics; D004573:Electrolytes; D013449:Sulfonamides; D000077786:Torsemide