LAUSR

OBJECTIVES The objective of the present study was to perform an external evaluation of published linezolid population pharmacokinetic and pharmacodynamic models, in order to evaluate the predictive performance using an independent dataset. Another aim was to offer an elegant environment for display and simulation of both the concentration and platelet count after linezolid administration. METHODS We performed a systematic literature search in PubMed for all studies evaluating the population pharmacokinetic and pharmacodynamic parameters of linezolid in patients, and selected the models to be used for the external validation. The bias of predictions was visually evaluated by plotting prediction errors (PE) and relative prediction errors (RPE). The precision of prediction was evaluated by calculating the mean absolute error (MAE), root mean squared error (RMSE), and mean relative error (MRE). RESULTS Three papers (Models A, B, and C) provided linezolid-induced platelet dynamic models using population pharmacokinetic and pharmacodynamic modelling approaches. The PE and RPE of both linezolid concentrations and platelet counts for Models A and C showed similar predictive distributions. With respect to the prediction accuracy of total linezolid concentration, the MAE, RMSE, and MRE of population prediction (PRED) values for Model C was the smallest. The comparison of the MAE, RMSE, and MRE of patient-individual prediction (IPRED) values for the three pharmacodynamic models revealed no large differences. CONCLUSION We confirmed the transferability of published population pharmacokinetic and pharmacodynamic models and showed that they were suitable for extrapolation to other hospitals and/or patients. The present study also introduced an application software based on Model C for the therapeutic drug monitoring of linezolid.