The role of glomerular filtration and active tubular secretion in predicting renal clearance of drugs in children using population pharmacokinetic and physiology-based pharmacokinetic modeling approaches: unspinning the yarn

Abstract

In this thesis population pharmacokinetic and physiologically-based pharmacokinetic (PBPK) approaches were applied to investigate the influence of glomerular filtration (GF) and active tubular secretion (ATS) on renal clearance in children. For this investigation, the contributions of passive (i.e. GF) and active (i.e. ATS) processes to renal clearance are considered. Both processes contribute to pediatric renal clearance and are expected to be influenced by developmental changes. Hence, the extent to which these developmental changes impact renal clearance is explored in pediatric populations using clinical data of existing drugs, and using a PBPK-based framework for hypothetical drugs with an array of different properties excreted by either GF or both GF and ATS. Pharmacolog