title: The Application of Physiologically Based Pharmacokinetic Modeling to Predict the Role of Drug Transporters: Scientific and Regulatory Perspectives.
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.
authors.affiliation: Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.|Current affiliation: Office of Generic Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: Yuzhuo
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: Vicky
authors.initials: V
authors.lastname: Hsu
authors.affiliation: Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: Manuela
authors.initials: M
authors.lastname: Grimstein
authors.affiliation: Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: Vikram
authors.initials: V
authors.lastname: Arya
authors.affiliation: Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: Vikram
authors.initials: V
authors.lastname: Sinha
authors.affiliation: Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Grillo
authors.affiliation: Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhao
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D005544:Forecasting; D006801:Humans; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000378:metabolism*; D014481:United States; D014486:United States Food and Drug Administration / Q000331:legislation & jurisprudence*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D026901:Membrane Transport Proteins; D004364:Pharmaceutical Preparations
keywords: drug-drug interaction; physiologically based pharmacokinetic models; predictive performance; transporter