Can the two-point method based on peak and trough concentrations accurately estimate the area under the curve of...

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.

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.

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.

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.