caa a22 4500 605533857 CHVBK 20210128100840.0 cr unu---uuuuu 210128e20150601xx s 000 0 eng 10.1007/s10928-015-9412-6 doi (NATIONALLICENCE)springer-10.1007/s10928-015-9412-6 Development of a paediatric population pharmacokinetic model for valacyclovir from literature non-compartmental values originating from sparse studies and Bayesian priors: a simulation study [Elektronische Daten] [Irene-Ariadne Kechagia, Aristides Dokoumetzidis] A preliminary population pharmacokinetic (PopPK) model of valacyclovir in children was developed from non-compartmental analysis (NCA) parameter values from literature, including several age groups, combined with Bayesian priors from a PopPK model of acyclovir, the active metabolite of valacyclovir, from literature too. Also a simulation study was carried out to evaluate the performance of various modelling choices related to the estimation of model parameters from NCA parameters originating from sparse PK studies. Assuming a one-compartment model with first order absorption, a mixed effects, meta-analysis approach was utilized which allows accounting the random intergroup variability, the detection of covariates and the application of informative Bayesian priors on the parameters. The conclusions from the simulation study calculating bias and precision for various cases, were that a model which takes explicitly into account the sampling schedule, performs better than a model using the theoretical expressions of calculating the NCA parameters. Also by using the geometric rather than the arithmetic means of NCA parameters, less biased results are obtained. These findings guided the choices for the valacyclovir model, for which informative priors from a PopPK model of acyclovir were applied for some of the parameters, in order to include a richer covariate model for clearance, not supported by the NCA dataset and a value for bioavailability. This preliminary valacyclovir model can be used in simulations to provide dosage recommendations for children of various ages and to help design more efficiently prospective clinical trials. Springer Science+Business Media New York, 2015 Bayesian priors nationallicence Meta-analysis nationallicence Paediatric pharmacokinetic model nationallicence Kechagia Irene-Ariadne School of Pharmacy, University of Athens, Panepistimiopolis, 15771, Athens, Greece aut Dokoumetzidis Aristides School of Pharmacy, University of Athens, Panepistimiopolis, 15771, Athens, Greece aut Journal of Pharmacokinetics and Pharmacodynamics Springer US; http://www.springer-ny.com 42/3(2015-06-01), 237-250 1567-567X 42:3<237 2015 42 10928 https://doi.org/10.1007/s10928-015-9412-6 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/s10928-015-9412-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kechagia Irene-Ariadne School of Pharmacy, University of Athens, Panepistimiopolis, 15771, Athens, Greece aut NATIONALLICENCE 700 1- Dokoumetzidis Aristides School of Pharmacy, University of Athens, Panepistimiopolis, 15771, Athens, Greece aut NATIONALLICENCE 773 0- Journal of Pharmacokinetics and Pharmacodynamics Springer US; http://www.springer-ny.com 42/3(2015-06-01), 237-250 1567-567X 42:3<237 2015 42 10928