ArticleThe AAPS journal2021
Understanding Mechanisms of Food Effect and Developing Reliable PBPK Models Using a Middle-out Approach.
Article in The AAPS journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed.
- Predicting Food Effect On Oral Drug Absorption For Solubility-Epithelial Membrane Permeation-Limited Cases With Bile Micelle Solubilization.Pharmaceutical research · 2025Article
- Indirect Modeling of Post-Prandial Intestinal Lymphatic Uptake of Halofantrine Using PBPK Approaches: Limitations and Implications.Pharmaceutics · 2025Article
- Physiologically Based Biopharmaceutics Model of Apixaban for Biopharmaceutics Risk Assessment.Pharmaceutics · 2025Article
- Article
- Using Mechanistic Modeling Approaches to Support Bioequivalence Assessments for Oral Products.The AAPS journal · 2024Review
- Streamlining Food Effect Assessment - Are Repeated Food Effect Studies Needed? An IQ Analysis.The AAPS journal · 2023Article
- Integrating Forward and Reverse Translation in PBPK Modeling to Predict Food Effect on Oral Absorption of Weakly Basic Drugs.Pharmaceutical research · 2023Article
- Physiologically Based Biopharmaceutics Modeling of Food Effect for Basmisanil: A Retrospective Case Study of the Utility for Formulation Bridging.Pharmaceutics · 2023Article
- Food and bile micelle binding of quaternary ammonium compounds.ADMET & DMPK · 2023Article
- Predicting Food Effects: Are We There Yet?The AAPS journal · 2022Article
- A PBPK Model of Ternary Cyclodextrin Complex of ST-246 Was Built to Achieve a Reasonable IV Infusion Regimen for the Treatment of Human Severe Smallpox.Frontiers in pharmacology · 2022Article
- In Vitro-In Silico Tools for Streamlined Development of Acalabrutinib Amorphous Solid Dispersion Tablets.Pharmaceutics · 2021Article
- The Impact of Diet and Exercise on Drug Responses.International journal of molecular sciences · 2021Review
- Use of Physiologically Based Pharmacokinetic Modeling for Predicting Drug-Food Interactions: Recommendations for Improving Predictive Performance of Low Confidence Food Effect Models.The AAPS journal · 2021Article
- On Absorption Modeling and Food Effect Prediction of Rivaroxaban, a BCS II Drug Orally Administered as an Immediate-Release Tablet.Pharmaceutics · 2021Article
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Over the last 10 years, 40% of approved oral drugs exhibited a significant effect of food on their pharmacokinetics (PK) and currently the only method to characterize the effect of food on drug absorption, which is recognized by the authorities, is to conduct a clinical evaluation. Within the pharmaceutical industry, there is a significant effort to predict the mechanism and clinical relevance of a food effect. Physiologically based pharmacokinetic (PBPK) models combining both drug-specific and physiology-specific data have been used to predict the effect of food on absorption and to reveal the underlying mechanisms. This manuscript provides detailed descriptions of how a middle-out modeling approach, combining bottom-up in vitro-based predictions with limited top-down fitting of key model parameters for clinical data, can be successfully used to predict the magnitude and direction of food effect when it is predicted poorly by a bottom-up approach. For nefazodone, a mechanistic clearance for the gut and liver was added, for furosemide, an absorption window was introduced, and for aprepitant, the biorelevant solubility was refined using multiple solubility measurements. In all cases, these adjustments were supported by literature data and showcased a rational approach to assess the factors limiting absorption and exposure.
Indexed as
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33398593What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.