Virtual bioequivalence assessment for two roxithromycin formulations using a physiologically based pharmacokinetic model

This study built and validated a roxithromycin physiologically based pharmacokinetic (PBPK) model to compare virtual bioequivalence (BE) between the test and reference formulations in East Asian populations. We collected roxithromycin’s physicochemical, in vitro and in vivo parameters from databases and published literature, then constructed an adult PBPK model via PK-Sim ® . The initial model was developed using clinical data from a 150 mg reference formulation and a comparative evaluation was conducted using clinical data from the test formulation. The precision of the PBPK model was evaluated by applying the mean fold error (MFE) approach to measure the difference between the predicted and observed values. After validation, formulation-specific in vitro dissolution data were imported to simulate PK profiles and virtual BE of the two products in identical virtual East Asian cohorts. The predicted concentration-time profiles following oral dosing matched with the observed data. For the AUC 0−t, C max , and T max parameters, more than 90% of the MFE ratios between predicted and observed values fell within the range of 0.5 to 2. Using the model to simulate the virtual bioequivalence of 99 virtual East Asian subjects demonstrated that the 90% confidence intervals (90% CI) for the geometric mean ratios of the primary pharmacokinetic parameters all fell within the range of 80%-125%. This study successfully developed and validated a PBPK model for roxithromycin. The virtual BE simulation results predicted the bioequivalence of the two roxithromycin formulations in 99 subjects. This study was registered at ClinicalTrials.gov (registration number: NCT06798051, retrospective registration on January 14, 2025).