This section contains only new information from FY2016. For background scientific information and outcomes from previous years on this research topic, please refer to the FY15 Regulatory Science Research Report on Physiologically-Based Absorption and Pharmacokinetic Models.

ORS staff facilitating research in this area

• Xinyuan Zhang, Jianghong Fan, Zhanglin Ni, Andrew Babiskin, Eleftheria Tsakalozou, Ross Walenga, Satish Sharan, and other ORS staff members

Projects and Collaborators

• Modernization of in vivo - in vitro oral bioperformance prediction and assessment. Gordon Amidon, University of Michigan
  • Site PI: James Brasseur
  • Contract #: HHSF223201310144C
• Physiologically based biopharmaceutics and pharmacokinetics of drug products for dermal absorption in humans, University of South Australia
  • Site PI: Michael Roberts
  • Grant #: 1U01FD005232-01
• Development and validation of dermal PBPK modelling platform towards virtual bioequivalence assessment considering population variability, Simcyp Ltd
  • Site PI: Sebastian Polak
  • Grant #: 1U01FD005225-01
• PBPK modeling and simulation for ocular dosage forms, Simulations Plus Inc
  • Site PI: Michael B Bolger
  • Grant #: 1U01FD005211-01
• An integrated multiscale-multiphysics modeling and simulation of ocular drug delivery with whole-body pharmacokinetic response, CFD Research Corporation
  • Site PI: Kay Sun
  • Grant #: 1U01FD005219-01
• Development of hybrid CFD-PBPK models for absorption of intranasal corticosteroids, Applied Research Associated, Inc.
  • Site PI: Jeff Schroeter
  • Grant #: 1U01FD005201-01
• A predictive multiscale computational tool for simulation of lung absorption and pharmacokinetics and optimization of pulmonary drug delivery, CFD Research Corporation
  • Site PI: Peng Guo
  • Grant #: 1U01FD005214-01
• Physiologically based pharmacokinetic model for drugs encapsulated into liposomes, University of North Carolina, Chapel Hill
  • Site PI: Yanguang Cao
  • Grant #: 1U01FD005206-01
• Assessment of intersubject variability of small airway delivery, University of Iowa (New)
  • Site PI: Ching-long Lin
  • Grant #: 1U01FD005837-01
• Enhancing the reliability, efficiency, and usability of Bayesian population PBPK modeling, Colorado State University (New)
  • Site PI: Brad Reisfeld
  • Grant #: 1U01FD005838-01
• Design, development, implementation and validation of a mechanistic physiologically-based pharmacokinetic (PBPK) framework for the prediction of the in vivo behavior of supersaturating drug products, Simcyp Ltd (New)
  • Site PI: David Barnes Turner
  • Grant #: 1U01FD005865-01

Publications

• Yousef S, Liu X, Mostafa A, Mohammed Y, Grice JE, Anissimov YG, Sakran W, Roberts MS. Estimating Maximal In Vitro Skin Permeation Flux from Studies Using Non-sink Receptor Phase Conditions. Pharm Res (Jun 16, 2016)
• Yousef S, Mohammed Y, Namjoshi S, Grice J, Sakran W, Roberts M. Mechanistic Evaluation of Hydration Effects on the Human Epidermal Permeation of Salicylate Esters. AAPS J (Sep 15, 2016)
• Chow EC, Talattof A, Tsakalozou E, Fan J, Zhao L, Zhang X. Using physiologically based pharmacokinetic (PBPK) modeling to evaluate the impact of pharmaceutical excipients on oral drug absorption: sensitivity analyses. AAPS J. (Aug 12, 2016)
• Lin H-P, Sun D, Zhang X, Wen H. Physiologically Based Pharmacokinetic Modeling for Substitutability Analysis of Venlafaxine Hydrochloride Extended-Release Formulations Using Different Release Mechanisms: Osmotic Pump Versus Openable Matrix. J Pharm Sci (2016)
• Schroeter JD, Stricklin D, Kimbell JS, Delvadia RR, and Zhang X. A physiologically-based pharmacokinetic model framework to estimate systemic bioavailability of fluticasone propionate nasal spray. Respiratory Drug Delivery 2016 Proceedings (2016)
• Schroeter JD, Kimbell JS, Saluja B, Delvadia RR, Vallorz III EL, and Sheth P. The impact of actuation force on droplet size distribution and spray duration of three commercially available nasal sprays. Respiratory Drug Delivery 2016 Proceedings (2016)
• Kimbell JS, Schroeter JD, Sheth P, Tian G, Delvadia RR, Saluja B, and Walenga R. Effect of actuation force on simulated regional nasal spray deposition in a healthy nasal cavity. Respiratory Drug Delivery 2016 Proceedings. (2016)
• Kannan et al, A Quasi-3D wire approach to model pulmonary airflow in human airways. International Journal for Numerical Methods in Biomedical Engineering, DOI: 10.1002/cnm.2838 (2016)

Presentations

• Bolger M. et al. Fluorometholone ocular suspension PBPK simulations using the OCAT^TM model in GastroPlus^TM. Global Technology Community Biotechnology (GTCbio), San Diego, CA (2015)
• He H, Wu Y, Liu C, Cao Y. Integrating Cellular Disposition of Doxorubicin into A Multiscale Physiologically Based Pharmacokinetic Model in Mice and Scale-up to Humans. ACoP Conference (2016)
• Lin HP, SunD, Zhang X, Wen H. Brand-generic substitutability analysis of venlafaxine hydrochloride extended-release tablets based on openable matrix and osmotic pump using PBPK modeling and simulation. AAPS Annual Meeting, Denver CO (2016)
• Sharan S, and Zhang X. Evaluation of Proton Pump Inhibitor (PPI) Effect for two Formulation of Paliperidone by Utilizing a Multi-pH Dissolution Model and Physiologically Based Pharmacokinetic (PBPK) Absorption Modeling and Simulation Approach. AAPS Annual Meeting, Denver CO (2016)
• Tsakalozou E, Sun D, Wen H, and Zhang X. In vitro-in vivo relationship development for oxybutynin chloride extended-release tablets to assess bioequivalence. AAPS Annual Meeting, Denver CO (2016)
• Fan J, Zhang X, Zhao L. Physiologically based pharmacokinetics (PBPK) absorption model to study the Impact of Salt-to-Base Conversion on Prasugrel HCl Bioequivalence in the Presence and Absence of Proton Pump Inhibitors. AAPS Annual Meeting, Denver CO (2016)
• Zhou T, Chow E, Wen H, Zhang X, Jiang W, Zhao L. Evaluation of the impact of in vitro release alterations on pharmacokinetics of metoprolol succinate extended-release (ER) tablets using the physiologically based pharmacokinetic (PBPK) absorption model. AAPS Annual Meeting, Denver CO (2016)
• Kimbell JS, Stricklin D, and Schroeter JD. Simulating nasal spray deposition: Effects of spray nozzle presence in the nasal vestibule. International Society for Aerosols in Medicine Conference, Munich, Germany, (May 30 – June 3, 2016). poster presentation
• Schroeter JD. Prediction II: Computational Fluid Dynamics, as part of a workshop titled Bridging the Gap from Science to Clinical Efficacy: Imaging, Modelling, and Physiology of Aerosols and the Lung. International Society for Aerosols in Medicine Conference, Munich, Germany, (May 30 – June 3, 2016). platform presentation
• Schroeter JD, Stricklin D, Kimbell JS, Delvadia RR, and Zhang X. A physiologically-based pharmacokinetic model framework to estimate systemic bioavailability of fluticasone propionate nasal spray. Respiratory Drug Delivery 2016, Scottsdale, AZ, (April 17-21, 2016). poster presentation
• Schroeter JD, Kimbell JS, Saluja B, Delvadia RR, Vallorz III EL, and Sheth P. The impact of actuation force on droplet size distribution and spray duration of three commercially available nasal sprays. Respiratory Drug Delivery 2016, Scottsdale, AZ, (April 17-21, 2016). poster presentation
• Kimbell JS, Schroeter JD, Sheth P, Tian G, Delvadia RR, Saluja B, and Walenga R. Effect of actuation force on simulated regional nasal spray deposition in a healthy nasal cavity. Respiratory Drug Delivery 2016, Scottsdale, AZ (April 17-21, 2016). poster presentation
• Invited talk: A Multiscale framework for Computational Inhalation Pharmacology. Kannan et al, 2nd International Conference on Respiratory & Pulmonary Medicine, Chicago, IL (Oct 17-18, 2016)
• Poster: A Multiscale Modeling Approach to Optimize Pulmonary Drug Delivery: 2nd International Conference on Respiratory & Pulmonary Medicine, Chicago, IL (Oct 17-18, 2016)

Outcomes

• FDA public workshop on Mechanistic Oral Absorption Modeling and Simulation for Formulation Development and Bioequivalence Evaluation (May 19, 2016)
• Six completed consults for ANDA reviews with PBPK modeling analysis
• Five product-specific guidances that utilized PBPK modeling analysis
• Three pre-ANDA meetings with industry with PBPK modeling analysis
• Two Citizen Petition responses with PBPK modeling analysis

ResourcesForYou

• Office of Generic Drugs FY 2016 Regulatory Science Research Report