title: Predictive Performance of Physiologically Based Pharmacokinetic and Population Pharmacokinetic Modeling of Renally Cleared Drugs in Children.
abstract: Predictive performance of physiologically based pharmacokinetic (PBPK) and population pharmacokinetic (PopPK) models of drugs predominantly eliminated through kidney in the pediatric population was evaluated. After optimization using adult clinical data, the verified PBPK models can predict 33 of 34 drug clearance within twofold of the observed values in children 1 month and older. More specifically, 10 of 11 of predicted clearance values were within 1.5-fold of those observed in children between 1 month and 2 years old. The PopPK approach also predicted 19 of 21 drug clearance within twofold of the observed values in children. In summary, our analysis demonstrated both PBPK and PopPK adult models, after verification with additional adult pharmacokinetic (PK) studies and incorporation of known ontogeny of renal filtration, could be applied for dosing regimen recommendation in children 1 month and older for renally eliminated drugs in a first-in-pediatric study.
authors: Quantitative Clinical Pharmacology, AstraZeneca, Waltham, Massachusetts, USA.
authors: W
authors: W
authors: Zhou
authors: Simcyp (A Certara Company), Sheffield, United Kingdom.
authors: T N
authors: TN
authors: Johnson
authors: Quantitative Clinical Pharmacology, AstraZeneca, Waltham, Massachusetts, USA.
authors: H
authors: H
authors: Xu
authors: Quantitative Clinical Pharmacology, AstraZeneca, Cambridge, United Kingdom.
authors: Sya
authors: S
authors: Cheung
authors: Quantitative Clinical Pharmacology, AstraZeneca, Waltham, Massachusetts, USA.
authors: K H
authors: KH
authors: Bui
authors: Quantitative Clinical Pharmacology, AstraZeneca, Waltham, Massachusetts, USA.
authors: J
authors: J
authors: Li
authors: Quantitative Clinical Pharmacology, AstraZeneca, Waltham, Massachusetts, USA.
authors: N
authors: N
authors: Al-Huniti
authors: Quantitative Clinical Pharmacology, AstraZeneca, Waltham, Massachusetts, USA. Diansong.Zhou@astrazeneca.com.
authors: D
authors: D
authors: Zhou
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D003198:Computer Simulation; D005260:Female; D005544:Forecasting; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects / Q000502:physiology*; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000097:blood* / Q000652:urine*
chemical_list: D004364:Pharmaceutical Preparations