Comparative Crossover, Randomized, Open-Label Bioequivalence Study on the Bioequivalence of Two Formulations of Thioctic Acid in Healthy Volunteers

Abstract

An open-label, randomized, crossover single-dose study, using two periods and two sequences with a washout period of seven days was conducted to assess the comparative bioavailability of thioctic (alpha-lipoic) acid (ALA) 600 mg formulation and that of a reference formulation. Blood samples were collected up to +6 h post dosing, the plasma was separated, and thioctic acid concentrations were determined by high-performance liquid chromatographic method with single mass spectrometry detection (HPLC-MS) and a lower limit of quantification of 190.1 ng/ml. Mean values of the individual Cmax were 1338.6 ± 751.8 ng/ml and 1215.8 ± 560.5 ng/ml for the test and reference preparations, respectively. Mean ± standard deviation (SD) total area under the curve up to the last measurable concentration (AUCt) was 3510.9 ± 1088.6 ng × h/ml for the test formulation and 3563.5 ± 1374.1 ng × h/ml for the reference formulation. Mean ± SD total area under the curve (AUCinf) was 6925.6 ± 4045.8 ng × h/ml for the test formulation and 7797.1 ± 5963.1 ng × h/ml for the reference preparation. Terminal elimination half-life was 5.68 ± 5.05 h for the test and 6.11 ± 6.15 h for the reference formulations. Time of maximum concentration (tmax) was 1.24 ± 1.23 h for the test and 2.05 ± 1.21 h for the reference formulations. Ninety percent confidence intervals were comprised within the bioequivalence acceptance criteria (80–125%) for all of the parameters analyzed except tmax. The comparison between males and females showed no significant difference for the two drug treatment.