Can the two-point method based on peak and trough concentrations accurately estimate the area under the curve of polymyxin B? A Monte Carlo simulation study.

Background: The area under the concentration‒time curve (AUC) is recognized as the therapeutic drug monitoring index of polymyxin B. The two-point method, which is based on peak and trough concentrations, is recommended for AUC estimation. However, its accuracy needs to be fully elucidated. Methods: A Monte Carlo simulation study was performed on published population pharmacokinetic (PPK) models. A series of plasma concentrations at steady state were simulated for each scenario. The performance of the two-point method was evaluated via mean absolute percent error (MAPE) and root mean square error (RMSE), with acceptable performance limits defined as ≤15% for the MAPE and ≤20% for the RMSE. Additionally, variations in infusion duration, body weight, and creatinine clearance were also investigated. Results: In the one-compartment model, the two-point method exhibits excellent predictive performance, characterized by both the MAPE and RMSE < 15%. For multicompartment models, prolonging the infusion duration markedly improved the accuracy of the two-point method, as demonstrated by a decrease in the average MAPE from 30.2% to 7.78% and in the average RMSE from 35.5% to 9.12% when comparing infusion durations of 0.5 h and 2 h. Body weight and creatinine clearance had limited influences on estimation accuracy in most models. Conclusion: The two-point method, which is based on peak and trough concentrations, represents a strong pharmacokinetic rationale and generate a testable hypothesis for the clinical application for estimating the AUC of polymyxin B. We suggest prolonging the infusion duration to ensure estimation accuracy in different patient settings.