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(beta) (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, two-sequence 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 ngxh/mL and 726.803 +/- 90.638 ngxh/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 bio-equivalent based on C-max and AUC(last).