Optimizing Linezolid Dosing in Lung Transplant Recipients: Population Pharmacokinetics, Target Attainment, and Thrombocytopenia Risk Assessment

The pharmacokinetic (PK) profiles of linezolid in lung transplant recipients (LTRs) differ from those in other patients. This study aimed to develop a population pharmacokinetic (PopPK) model to evaluate dosage regimens based on various biological covariates and assess the risk of thrombocytopenia. The nonlinear mixed-effects modeling method was employed to establish the PopPK model. Monte Carlo simulations assessed the probability of target attainment (PTA) under different covariates and minimum inhibitory concentration (MIC) ranges. The study included 43 LTRs with 142 linezolid concentration-time data points. The final model identified estimated glomerular filtration rate and tacrolimus trough level as key covariates for apparent clearance. The 300 mg bid regimen maintained peak and trough concentrations within the 2-8 mg/L range, while the 600 mg qd dosing group achieved a PTA greater than 80% across an MIC range of 0.25-1 mg/L. Linezolid C_min impacted platelet levels, with baseline levels influencing the severity of reduction. This PopPK model offers valuable insights for optimizing linezolid dosing, considering immunosuppressant therapy and thrombocytopenia risk, and serves as a reference for dose selection in post-surgical LTRs.