Determination of carvedilol concentrations Plasma concentrations of carvedilol were determined using a validated high-performance liquid chromatography (HPLC) coupled with the tandem mass spectrometry method. The sample extracts were analyzed using HPLC (Agilent 1200; Agilent, Waldbronn, Germany) and a Synergi 4 μ Polar-RP 80 Å column (4.0 μm, 100×2.0 mm; Phenomenex, Torrance, CA, USA) with mobile phase consisting of ammonium formate and acetonitrile with methanol (, v/v). Using this assay, interday accuracy ranged from 100.35% to 110.73%, and interday precision, expressed as percent coefficient of variation (%CV), ranged from 3.82% to 12.92%.In addition, intraday accuracy and precision (%CV) ranged from 102.31% to 106.93%, and from 3.10% to 10.02%, respectively.Demographic data and pharmacokinetic parameters were summarized using descriptive statistics.The dose proportionality of carvedilol over the dose range 8–128 mg was assessed by fitting a power model.In varying sequences, each subject received three of five carvedilol SR formulations (8, 16, 32, 64, or 128 mg once).
S86168 Checked for plagiarism Yes Review by Single-blind Peer reviewer comments 7 Editor who approved publication: Professor Shu-Feng Zhou Chong Kun Dang Clinical Research and Clinical Epidemiology and Medical Information, CKD Pharmaceuticals, Seoul, Republic of Korea Background: Carvedilol is a third-generation β-blocker indicated for congestive heart failure and high blood pressure.
On days 2 (36 h after dosing) and 3 (48 h after dosing), subjects were asked to revisit the CTC to assess the tolerability and pharmacokinetics of carvedilol.
The schedule for the second and third treatment period procedures was the same as in the first period.
The aim of this study was to investigate the dose proportionality of the carvedilol sustained-release (SR) formulation in healthy male subjects.
Methods: An open-label, single dose-ascending, 10-sequence, 3-period balanced incomplete block study was performed using healthy male subjects.