Evidence map›Paper›PMID 39899201›Full record

ArticleClinical pharmacokinetics2025

Evaluation of Solubility-Limited Absorption as a Surrogate to Predicting Positive Food Effect of BCS II/IV Drugs.

Karine Rodriguez-Fernandez, José David Gómez-Mantilla, Suneet Shukla, Peter Stopfer, Peter Sieger, Victor Mangas-Sanjuán, Sheila Annie Peters

Abstract read
In one paragraph

Article in Clinical pharmacokinetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Co-amorphization for solubility and dissolution rate improvement: the case of low-crystallization-tendency drugs.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2026
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Karine Rodriguez-FernandezDepartment of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia, Valencia, Spain.ORCID 0009-0008-2065-7188
José David Gómez-MantillaTranslational Medicine and Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH & Co. KG, Binger Straße 173, 55216, Ingelheim am Rhein, Germany.
Suneet ShuklaTranslational Medicine and Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH & Co. KG, Binger Straße 173, 55216, Ingelheim am Rhein, Germany.
Peter StopferTranslational Medicine and Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH & Co. KG, Binger Straße 173, 55216, Ingelheim am Rhein, Germany.
Peter SiegerDrug Discovery Sciences, Boehringer Ingelheim Pharma GmbH & Co. KG, 88397, Biberach a.d. Riss, Germany.
Victor Mangas-SanjuánDepartment of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia, Valencia, Spain.ORCID 0000-0002-2503-3373
Sheila Annie PetersTranslational Medicine and Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH & Co. KG, Binger Straße 173, 55216, Ingelheim am Rhein, Germany. sheila.peters@boehringer-ingelheim.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

INTRODUCTION AND

objectivePhysiologically based pharmacokinetic (PBPK) models are increasingly used to predict food effect (FE) but model parameterization is challenged by in vitro-in vivo (IVIV) disconnect and/or parameter nonidentifiability. To overcome these issues, we propose a simplified PBPK model, in which all solubility-driven processes are lumped into a single parameter, solubility, which is optimized against observed concentration-time data.

methodsA set of commercially available biopharmaceutical classification system (BCS) II/IV compounds was selected to measure the solubility in a fasted state simulated intestinal fluid (FaSSIF) medium. The compounds were ranked from the lowest to the highest dose-adjusted FaSSIF solubility (FaSSIF/D) value and subdivided into three areas based on an upper and a lower limit: drugs with FaSSIF/D > upper limit having no FE, drugs with FaSSIF/D < lower limit having FE, and drugs between the limits said to be in the sensitivity range (SR), for which we tested the hypothesis that solubility-limited absorption (SLA) identified by simplified PBPK model can reliably predict positive FE if their exposures are not impacted by gut efflux or gut metabolism.

resultsWe demonstrate, using a subset of drugs within SR for which PBPK models were available, that drugs with SLA exhibited a positive FE, while those with no SLA did not show FE.

conclusionsThis proposal allows for a reliable binary prediction of FE to enable timely decisions on the need for pilot FE studies as well as the timing of pivotal FE studies.

Indexed as

Food-Drug InteractionsIntestinal AbsorptionModels, BiologicalBiopharmaceuticsFastingHumansPharmaceutical PreparationsPharmacokineticsSolubilityPharmaceutical Preparations

Identifiers

PMID39899201
PMCPMC11954708

What Socratic holds

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Registered trials

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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 Socratic graph.