Predictive Performance of Physiologically Based Pharmacokinetic and Population Pharmacokinetic Modeling of Renally Cleared Drugs in Children.
CPT Pharmacometrics Syst Pharmacol
; 5(9): 475-83, 2016 09.
Article
em En
| MEDLINE
| ID: mdl-27566992
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.
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Base de dados:
MEDLINE
Assunto principal:
Simulação por Computador
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Preparações Farmacêuticas
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Taxa de Depuração Metabólica
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Rim
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Modelos Biológicos
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article