The Application of Physiologically Based Pharmacokinetic Modeling to Predict the Role of Drug Transporters: Scientific and Regulatory Perspectives
| Autor: | Yuzhuo Pan, Joseph A. Grillo, Vikram Sinha, Manuela Grimstein, Ping Zhao, Lei Zhang, Vicky Hsu, Vikram Arya |
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| Rok vydání: | 2016 |
| Předmět: |
Pharmacology
Drug Physiologically based pharmacokinetic modelling Clinical pharmacology media_common.quotation_subject Pharmacokinetic modeling Transporter Computational biology Drug action Biology 030226 pharmacology & pharmacy law.invention Food and drug administration 03 medical and health sciences 0302 clinical medicine Pharmacokinetics law 030220 oncology & carcinogenesis Pharmacology (medical) media_common |
| Zdroj: | The Journal of Clinical Pharmacology. 56:S122-S131 |
| ISSN: | 0091-2700 |
| DOI: | 10.1002/jcph.740 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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