Population pharmacokinetic analysis of eperisone in healthy Korean volunteers
Eperisone, an oral muscle relaxant utilized for musculoskeletal disorders, displays considerable pharmacokinetic (PK) variability in bioequivalence investigations. This study aimed to delineate the PK profile of eperisone following oral administration to Korean volunteers using both non-compartmental and population analysis methods. A dataset comprising 360 concentration-time measurements obtained from 15 healthy volunteers during a bioequivalence study of eperisone 50 mg (Murex®) was utilized for PK analysis. Non-compartmental analysis was executed with WinNonLinTM, while population analysis was conducted using NONMEM®. Thirty demographic and pathophysiological characteristics were investigated for their potential influence on eperisone PKs. Non-compartmental analysis revealed mean eperisone t1/2, CL/F, and Vz/F values of 3.81 hours, 39.24×103 L/h, and 197.23×103 L, respectively. Population PK modeling identified a two-compartment model with first-order absorption (typical population Ka = 1.5 h-1) and first-order elimination (typical population CL/F and Vc/F = 30.8×103 L/h and 86.2×103 L, respectively) as the best fit for eperisone PKs. Inter-individual variability in CL/F and Vc/F was estimated at 87.9% and 130.3%, respectively, while inter-occasion variability in CL/F and Vc/F was estimated at 23.8% and 30.8%, respectively. Aspartate aminotransferase levels and smoking status were identified as potential covariates influencing the CL/F of eperisone. This study represents the first attempt to develop a disposition model for eperisone and assess the impact of covariates on its pharmacokinetic variability.
2024 Spring Convention