Title [character count: 150 incl. spaces; max. 150 incl. spaces] Bottom-up meets top-down: Complementary PBPK and PopPK modeling for regulatory approval of a dosing algorithm of valganciclovir in very young children Authors K Jorga 1 , C Chavanne 2 , N Frey 2 , T Lave 3 , V Lukacova 4 , N Parrott 3 , R Peck 2 and B Reigner 2 1 KarinJorga Life Science Consulting GmbH, Basel, Switzerland; 2 Pharma Research & Development, Clinical Pharmacology, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland; 3 Pharma Research & Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland; 4 SimulationsPlus, Inc., Lancaster, California, USA. Correspondence: B Reigner, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland; Tel: +41 61 688 45 07; Email: bruno.reigner@roche.com. Word count (max. 4,000 words excl. abstract, references, tables, and figures): 3999 Number of references (max. 50): 50 Number of tables/figures (max. 7): 7 (4 tables, 3 figures) Key words: Pharmacokinetics, dose, algorithm, neonatal, pediatric, modeling, simulation, population pharmacokinetics, physiologically-based pharmacokinetics, regulatory This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as an ‘Accepted Article’, doi: 10.1002/cpt.449 This article is protected by copyright. All rights reserved.