The misspecified model provided biased PK/PD target information (e.g. Meropenem as a short half-life drug (~1 h) was more affected than caspofungin (~ 9–11 h). On the individual level, the rBias of the planned scenario for the typical values V1, Q and V2 increased with increasing uncertainty in time, while CL, AUC and elimination half-life were least affected. Results: On the population level, the estimates of the proportional residual error (prop.-err.) and the interindividual variability (IIV) on the central volume of distribution (V1) were most affected by erroneous records in the sampling and infusion time (e.g. The accurate and the misspecified (using planned sampling times) model were used for Bayesian forecasting of meropenem to assess the impact on PK/PD target calculations relevant to dosing decisions. Relative bias (rBias) and root mean squared error (rRMSE) were calculated to determine accuracy and precision of the primary and secondary PK parameters on the population and individual level. The estimation step was then performed with the accurate or planned times (replacing real time points by scheduled study values).
deviation between accurate and planned sampling and infusion times (standard deviation (SD) ± 5 min to ± 30 min) were added randomly in R before carrying out the simulation step. Methods: A stochastic simulation and estimation study was performed in NONMEM ® using previously published population PK models of meropenem and caspofungin.
The aim of this study was to investigate uncertain documentation of (i) sampling times and (ii) infusion rate exemplified with two anti-infectives. The impact of uncertainty in documented sampling and infusion times in population PK modeling and model-informed precision dosing have not yet been systematically evaluated.
4Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germanyīackground: Routine clinical TDM data is often used to develop population pharmacokinetic (PK) models, which are applied in turn for model-informed precision dosing.3Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.2Department of Clinical Pharmacy, Institute of Pharmacy, University of Hamburg, Hamburg, Germany.1Department of Hospital Pharmacy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.Dzenefa Alihodzic 1,2, Astrid Broeker 2, Michael Baehr 1, Stefan Kluge 3, Claudia Langebrake 1,4 and Sebastian Georg Wicha 2*
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