Pharmacokinetic and bioequivalence study of sugar-coated and film-coated eperisone tablets in healthy subjects: A randomized, open-label, three-way, reference-replicated crossover study

Objective: Eperisone hydrochloride is used in the treatment of musculoskeletal disorders as a muscle relaxant via blocking of calcium channels. In this study, we aimed to investigate the within-subject variability (CVwR) of reference eperisone formulation for highly-variable drugs and to perform bioequivalence study of two oral formulations (sugar- and film-coated tablets) of eperisone hydrochloride 50 mg in healthy subjects by reference-replicated crossover study. Materials and methods: 36 healthy Korean male subjects were recruited, and 33 subjects completed the study. A randomized, single-dose, open-label, three-way, three-sequence, reference formulation-replicated, crossover bioequivalence study was conducted to determine the bioequivalence of eperisone. Blood samples were collected before dosing and at 0.33, 0. 67, 1, 1.5, 2, 2.5. 3, 4, 6, 8, and 12 hours after dosing. The plasma concentration of eperisone was determined using liquid chromatography-tandem mass spectrometry. Results: The CV(wR )of eperisone reference product was 33.17% for AUC(1) and 50.21% for C-max. The acceptance limit for C(max )was scaled to 0.6984 - 1.4319 according to CVwR. The 90% confidence intervals for the test/reference geometric mean ratio were 0.8275 - 1.1692 for AUC(1) and 0.7587 - 1.1652 for C(max )which were within the accepted bioequivalence limits. Single oral doses of eperisone hydrochloride 50 mg were generally well tolerated in healthy adult subjects in this study. Conclusion: The newly developed film-coated tablet can be interchanged with the original sugar-coated tablet of eperisone. In addition. the reference scaling methods arc more effective and economical than the classical method for assessing BE of HVDs.