Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2018 Feb;7(2):82-89.
doi: 10.1002/psp4.12260. Epub 2017 Nov 23.

Predictive Performance of Physiologically Based Pharmacokinetic Models for the Effect of Food on Oral Drug Absorption: Current Status

Mengyao Li  1   2 , Ping Zhao  1   3 , Yuzhuo Pan  4 , Christian Wagner  1   5
Affiliations
Review

Predictive Performance of Physiologically Based Pharmacokinetic Models for the Effect of Food on Oral Drug Absorption: Current Status

Mengyao Li et al. CPT Pharmacometrics Syst Pharmacol. 2018 Feb.

Abstract

A comprehensive search in literature and published US Food and Drug Administration reviews was conducted to assess whether physiologically based pharmacokinetic (PBPK) modeling could be prospectively used to predict clinical food effect on oral drug absorption. Among the 48 resulted food effect predictions, ∼50% were predicted within 1.25-fold of observed, and 75% within 2-fold. Dissolution rate and precipitation time were commonly optimized parameters when PBPK modeling was not able to capture the food effect. The current work presents a knowledgebase for documenting PBPK experience to predict food effect.

PubMed Disclaimer

Figures

Figure 1
Figure 1
A general workflow to use physiologically based pharmacokinetic (PBPK) model to predict food effect (FE) based on cases analyzed. *Vd was individually fitted to clinical pharmacokinetic (PK) data under fasted and fed states in Shono et al.14 (2009) and Shono et al.15 (2010). CL was separately fitted to clinical PK data under fasted and fed states in Shono et al.14 (2009). GI, gastrointestinal.
Figure 2
Figure 2
Pie chart of Biopharmaceutics Classification System (BCS) class distribution for 27 compounds (n, % total).
Figure 3
Figure 3
Pie chart of physiologically based pharmacokinetic (PBPK) model platforms (absorption models) used in the 15 documents (n, % total). ACAT, Advanced Compartmental Absorption and Transit; ADAM, advanced dissolution, absorption, and metabolism.
Figure 4
Figure 4
Predictive performance assessment of physiologically based pharmacokinetic (PBPK) models that had prospective predictions. (a) Predicted area under the concentration‐time ratio (AUCR) vs. observed AUCR. (b) Predicted peak plasma concentration ratio (CmaxR) vs. the observed CmaxR. (c) Predicted time of maximum plasma concentration ratio (tmaxR) vs. the observed tmaxR. The red solid lines in all plots are lines of identity (y = x). Red dashed lines in all plots represent y = 0.8x and y = 1.25x. Blue dashed in all plots represent y = 1.25 and x = 1.25. Pink dotted lines in all plots represent y = 0.5x and y = 2x. BCS, Biopharmaceutics Classification System. NA, Not Available.
Figure 5
Figure 5
Summary of predictive performance (prospective predictions, left) and optimization cases (right) to match observed food effect (FE). AUCR, area under the concentration‐time ratio; PBPK, physiologically based pharmacokinetic; PK, pharmacokinetic.
See this image and copyright information in PMC

References

    1. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER). Guidance for Industry ‐ Food‐Effect Bioavailability and Fed Bioequivalence Studies. <https://www.fda.gov/downloads/regulatoryinformation/guidances/ucm126833.pdf> (2002).
    1. Rose, R.H. , Turner, D.B. , Neuhoff, S. & Jamei, M. Incorporation of the time‐varying postprandial increase in splanchnic blood flow into a PBPK model to predict the effect of food on the pharmacokinetics of orally administered high‐extraction drugs. AAPS J. 19, 1205–1217 (2017). - PubMed
    1. Lentz, K.A. Current methods for predicting human food effect. AAPS J. 10, 282–288 (2008). - PMC - PubMed
    1. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER). Guidance for Industry – Bioequivalence Studies with Pharmacokinetic Endpoints for Drugs Submitted Under an ANDA. <https://www.fda.gov/downloads/drugs/guidances/ucm377465.pdf> (2013).
    1. Fleisher, D. , Li, C. , Zhou, Y. , Pao, L.H. & Karim, A. Drug, meal and formulation interactions influencing drug absorption after oral administration. Clinical implications. Clin. Pharmacokinet. 36, 233–254 (1999). - PubMed

Publication types

Substances