caa a22 4500 605533822 CHVBK 20210128100840.0 cr unu---uuuuu 210128e20151201xx s 000 0 eng 10.1007/s10928-015-9428-y doi (NATIONALLICENCE)springer-10.1007/s10928-015-9428-y A pharmacometric case study regarding the sensitivity of structural model parameter estimation to error in patient reported dosing times [Elektronische Daten] [Jonathan Knights, Shashank Rohatagi] Although there is a body of literature focused on minimizing the effect of dosing inaccuracies on pharmacokinetic (PK) parameter estimation, most of the work centers on missing doses. No attempt has been made to specifically characterize the effect of error in reported dosing times. Additionally, existing work has largely dealt with cases in which the compound of interest is dosed at an interval no less than its terminal half-life. This work provides a case study investigating how error in patient reported dosing times might affect the accuracy of structural model parameter estimation under sparse sampling conditions when the dosing interval is less than the terminal half-life of the compound, and the underlying kinetics are monoexponential. Additional effects due to noncompliance with dosing events are not explored and it is assumed that the structural model and reasonable initial estimates of the model parameters are known. Under the conditions of our simulations, with structural model CV% ranging from ~20 to 60%, parameter estimation inaccuracy derived from error in reported dosing times was largely controlled around 10% on average. Given that no observed dosing was included in the design and sparse sampling was utilized, we believe these error results represent a practical ceiling given the variability and parameter estimates for the one-compartment model. The findings suggest additional investigations may be of interest and are noteworthy given the inability of current PK software platforms to accommodate error in dosing times. Springer Science+Business Media New York, 2015 Population pharmacokinetics nationallicence Simulation nationallicence Dosing inaccuracies nationallicence Reporting error nationallicence Parameter Estimation nationallicence Knights Jonathan Otsuka Pharmaceutical Development & Commercialization, Inc., 508 Carnegie Center Blvd. Suite 300, 08540, Princeton, NJ, USA aut Rohatagi Shashank Otsuka Pharmaceutical Development & Commercialization, Inc., 508 Carnegie Center Blvd. Suite 300, 08540, Princeton, NJ, USA aut Journal of Pharmacokinetics and Pharmacodynamics Springer US; http://www.springer-ny.com 42/6(2015-12-01), 627-637 1567-567X 42:6<627 2015 42 10928 https://doi.org/10.1007/s10928-015-9428-y text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10928-015-9428-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Knights Jonathan Otsuka Pharmaceutical Development & Commercialization, Inc., 508 Carnegie Center Blvd. Suite 300, 08540, Princeton, NJ, USA aut NATIONALLICENCE 700 1- Rohatagi Shashank Otsuka Pharmaceutical Development & Commercialization, Inc., 508 Carnegie Center Blvd. Suite 300, 08540, Princeton, NJ, USA aut NATIONALLICENCE 773 0- Journal of Pharmacokinetics and Pharmacodynamics Springer US; http://www.springer-ny.com 42/6(2015-12-01), 627-637 1567-567X 42:6<627 2015 42 10928