popPK analysis
In this study, a popPK model of contezolid acefosamil in healthy Chinese subjects was constructed, which preliminarily investigated the factors affecting the PK of contezolid acefosamil. The data of the popPK model for contezolid acefosamil were derived from healthy Chinese subjects (all data of the IV cohorts), and the active ingredient contezolid was mainly considered during the modeling. The model was constructed using the non-linear mixed effects model of Phoenix (Certara, LP, Princeton, NJ, USA). The basic structural model mainly investigated the one-, two-, and three-compartment models. The exponential model was adopted for examining the inter-individual variability. The additive, proportional, and mixed residual error models were used for investigating the intra-individual variability. The covariates to be included were preliminarily screened by correlation analysis on covariates and various system parameters. The covariates include demographic variables (age, body weight, gender, BMI, and body height) and clinical laboratory tests (hemoglobin, platelet count, albumin, total protein, hematocrit, alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, total bilirubin, direct bilirubin, and creatinine). Forward selection and backward elimination methods were adopted in the covariate screening process. A covariate was selected when the objective function value (OFV) decreased by more than 6.63 after forward selection. A covariate was eliminated from the model when the OFV increased by less than 10.83 after backward elimination. The final model was determined according to parameter estimation precision, GOF plot, and OFV.