Applicability of a Single Time Point Strategy for the Prediction of Area Under the Concentration Curve of Linezolid in Patients: Superiority of C trough - over C max -Derived Linear Regression Models

Background and Objectives Linezolid, a oxazolidinone, was the first in class to be approved for the treatment of bacterial infections arising from both susceptible and resistant strains of Gram-positive bacteria. Since overt exposure of linezolid may precipitate serious toxicity issues, therapeutic drug monitoring (TDM) may be required in certain situations, especially in patients who are prescribed other co-medications. Methods Using appropriate oral pharmacokinetic data (single dose and steady state) for linezolid, both maximum plasma drug concentration ( C max ) versus area under the plasma concentration–time curve (AUC) and minimum plasma drug concentration ( C min ) versus AUC relationship was established by linear regression models. The predictions of the AUC values were performed using published mean/median C max or C min data and appropriate regression lines. The quotient of observed and predicted values rendered fold difference calculation. The mean absolute error (MAE), root mean square error (RMSE), correlation coefficient ( r ), and the goodness of the AUC fold prediction were used to evaluate the two models. Results The C max versus AUC and trough plasma concentration ( C trough ) versus AUC models displayed excellent correlation, with r values of >0.9760. However, linezolid AUC values were predicted to be within the narrower boundary of 0.76 to 1.5-fold by a higher percentage by the C trough (78.3 %) versus C max model (48.2 %). The C trough model showed superior correlation of predicted versus observed values and RMSE ( r = 0.9031; 28.54 %, respectively) compared with the C max model ( r = 0.5824; 61.34 %, respectively). Conclusions A single time point strategy of using C trough level is possible as a prospective tool to measure the AUC of linezolid in the patient population.