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The Application of Physiologically Based Pharmacokinetic Modeling to Predict the Role of Drug Transporters: Scientific and Regulatory Perspectives
Author(s) -
Pan Yuzhuo,
Hsu Vicky,
Grimstein Manuela,
Zhang Lei,
Arya Vikram,
Sinha Vikram,
Grillo Joseph A.,
Zhao Ping
Publication year - 2016
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/jcph.740
Subject(s) - physiologically based pharmacokinetic modelling , transporter , drug , pharmacology , pharmacokinetics , clinical pharmacology , drug metabolism , drug action , computational biology , chemistry , medicine , biology , biochemistry , gene
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.