Pharmacokinetic comparisons of two acetyl-L-carnitine formulations in healthy Korean volunteers

Background: Acetyl-L-carnitine (ALC) has demonstrated neuroprotective effects in several experiments and is widely prescribed to reduce cognitive impairment in Alzheimer's disease patients or manage neuropathic symptoms in diabetic patients. Objectives: This study was designed to assess the pharmacokinetic (PK) bioequivalence between a new generic (test) formulation of ALC hydrochloride 590 mg and a branded (reference) formulation of ALC hydrochloride 590 mg in healthy Korean male volunteers. Methods: This was a randomized-sequence, single-dose, two-way crossover study. All subjects randomly received one formulation of the test or reference tablet and the other formulation with a 7-day washout period. Blood samples (7 mL) were collected immediately before dosing, and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, and 12 hours postdose. The plasma concentrations of ALC were analyzed using liquid chromatography tandem mass spectrometry. Tolerability was assessed throughout the study. Results: The PK profiles of both formulations showed similar trends. The mean (+/- SD) baseline (predose) concentration of ALC was 1.23 +/- 0.31 p,g/ mL and 1.09 +/- 0.30 irg/mL for the test and the reference formulations, respectively. The mean C-max for the test and reference formulations were 1.74 +/- 0.43 mu g/mL and 1.68 +/- 0.48 mu g/mL, respectively. The mean AUC(last) of ALC was 12.96 +/- 1.89 mu gxh/mL and 12.49 +/- 2.44 mu gxh/mL for the test and reference formulations, respectively. The geometric mean ratios of test/reference (90% CI) were 1.050 (0.960 - 1.149) for C-max and 1.048 (1.000 - 1.099) for AUC(last). Both formulations were well tolerated in all treatment groups. Conclusion: The test and the reference formulations of ALC were bioequivalent with regard to the PK parameters.