Impact of unbound fraction variations on model evaluation
To
reflect what has been reported in
the literature for piperacillin unbound fraction levels among critically
ill patients, total concentrations obtained were applied an unbound
fraction ranging from 50 to 100%, by increments of 5% [3, 13, 14].
Afterwards, piperacillin predicted concentrations were obtained by using
a previously validated population PK (popPK) model and by using mean
population estimates reported by the authors [15]. Prediction error
(PE, equation 1) was calculated to assess the predictive performance of
the model by comparing predicted concentrations with observed
concentrations after application of an unbound fraction [16]. Model
bias was determined with median prediction error (MDPE, equation 2) and
model imprecision was determined with the median absolute prediction
error (MDAPE, equation 3) [17]. The predictive performance of the
model was acceptable if MDPE was between ± 20% and if MDAPE ≤ 30%.
Predicted concentrations were obtained using NONMEM version 7.5 (ICON
Development Solutions, Ellicott City, MD, USA), and calculations were
performed on R version 4.1.2 using RStudio interface version 1.4.1717.