The Application of Physiologically Based Pharmacokinetic Modeling to Predict the Role of Drug Transporters: Scientific and Regulatory Perspectives.
J Clin Pharmacol
; 56 Suppl 7: S122-31, 2016 07.
Article
em En
| MEDLINE
| ID: mdl-27385170
ABSTRACT
Transporters play an important role in drug absorption, disposition, and drug action. The evaluation of drug transporters requires a comprehensive understanding of transporter biology and pharmacology. Physiologically based pharmacokinetic (PBPK) models may offer an integrative platform to quantitatively evaluate the role of drug transporters and its interplay with other drug disposition processes such as passive drug diffusion and elimination by metabolizing enzymes. To date, PBPK modeling and simulations integrating drug transporters lag behind that for drug-metabolizing enzymes. In addition, predictive performance of PBPK has not been well established for predicting the role of drug transporters in the pharmacokinetics of a drug. To enhance overall predictive performance of transporter-based PBPK models, it is necessary to have a detailed understanding of transporter biology for proper representation in the models and to have a quantitative understanding of the contribution of transporters in the absorption and metabolism of a drug. This article summarizes PBPK-based submissions evaluating the role of drug transporters to the Office of Clinical Pharmacology of the US Food and Drug Administration.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Membrana Transportadoras
/
United States Food and Drug Administration
/
Preparações Farmacêuticas
/
Modelos Biológicos
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Animals
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Humans
País/Região como assunto:
America do norte
Idioma:
En
Revista:
J Clin Pharmacol
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Estados Unidos