Pharmacokinetic comparison and bioequivalence evaluation of two 10-mg baclofen formulations in healthy male subjects

Backgrounds: Baclofen is used as a skeletal muscle relaxant for multiple sclerosis patients. It depresses the transmission of monosynaptic and polysynaptic reflex by stimulating GABA_β (gamma-aminobutyric acid) receptors. Objectives: The aim of this study was to compare the pharmacokinetic characteristics of two 10-mg baclofen formulations and to assess bioequivalence. Methods: A randomized, single-dose, two-period, twosequence crossover study was conducted in healthy male subjects. Each subject received the test or reference formulations. After washout period, all subjects received the alternative formulation. Blood samples were collected for up to 24 hours after the dose in each period. Pharmacokinetic (PK) parameters, including t_max, C_max, and AUC_last were calculated by noncompartmental methods. The geometric mean ratio (GMR) of the test to the reference formulation and its 90% confidence interval (CI) for C_max and AUC_last were calculated for assessment of bioequivalence. Results: A total of 22 subjects completed the study. The median t_max of the test and the reference formulation were 1.50 and 1.25 hours, respectively. The mean (± SD) C_max of the test and the reference formulation were 141.401 ± 29.447 ng/ mL and 138.837 ± 31.392 ng/mL, respectively. The mean (± SD) AUC_last of the two formulations were 702.404 ± 82.149 ng×h/mL and 726.803 ± 90.638 ng×h/mL, respectively. The GMR (90% CI) of the test to the reference formulation for the C_max and AUC_last were 1.0306 (0.9564 - 1.1106) and 0.9674 (0.9437 - 0.9916), respectively. Conclusions: The two different baclofen 10-mg formulations had similar PK profiles and were bioequivalent based on C_max and AUC_last.