Optimized sampling to estimate vancomycin drug exposure: Comparison of pharmacometric and equation-based approaches in a simulation-estimation study.

Vancomycin dosing should be accompanied by area under the concentration-time curve (AUC)-guided dosing using model-informed precision dosing software according to the latest guidelines. Although a peak plus a trough sample is considered the gold standard to determine the AUC, single-sample strategies might be more economic. Yet, optimal sampling times for AUC determination of vancomycin have not been systematically evaluated. In the present study, automated one- or two-sample strategies were systematically explored to estimate the AUC with a model averaging and a model selection algorithm. Both were compared with a conventional equation-based approach in a simulation-estimation study mimicking a heterogenous patient population (n = 6000). The optimal single-sample timepoints were identified between 2-6.5 h post dose, with varying bias values between -2.9% and 1.0% and an imprecision of 23.3%-24.0% across the population pharmacokinetic approaches. Adding a second sample between 4.5-6.0 h improved the predictive performance (-1.7% to 0.0% bias, 17.6%-18.6% imprecision), although the difference in the two-sampling strategies were minor. The equation-based approach was always positively biased and hence inferior to the population pharmacokinetic approaches. In conclusion, the approaches always preferred samples to be drawn early in the profile (<6.5 h), whereas sampling of trough concentrations resulted in a higher imprecision. Furthermore, optimal sampling during the early treatment phase could already give sufficient time to individualize the second dose, which is likely unfeasible using trough sampling.