Forecasting oral absorption across biopharmaceutics classification system classes with physiologically based pharmacokinetic models

Hansmann, Simone; Darwich, Adam; Margolskee, Alison; Aarons, Leon; Dressman, Jennifer

doi:10.1111/jphp.12618

Cited by 38Drug Solubulity and Delivery SystemsPharmaceutical studies and practicesComputational Drug Discovery Methods

Forecasting oral absorption across biopharmaceutics classification system classes with physiologically based pharmacokinetic models

Hansmann, Simone, Darwich, Adam, Margolskee, Alison, Aarons, Leon, Dressman, Jennifer·2016·Journal of Pharmacy and Pharmacology

DOI 10.1111/jphp.12618

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Abstract

Objectives: The aim of this study was (1) to determine how closely physiologically based pharmacokinetic (PBPK) models can predict oral bioavailability using a priori knowledge of drug-specific properties and (2) to examine the influence of the biopharmaceutics classification system class on the simulation success. Methods: Simcyp Simulator, GastroPlus™ and GI-Sim were used. Compounds with published Biowaiver monographs (bisoprolol (BCS I), nifedipine (BCS II), cimetidine (BCS III), furosemide (BCS IV)) were selected to ensure availability of accurate and reproducible data for all required parameters. Simulation success was evaluated with the average fold error (AFE) and absolute average fold error (AAFE). Parameter sensitivity analysis (PSA) to selected parameters was performed. Key findings: Plasma concentration–time profiles after intravenous administration were forecast within an AAFE < 3. The addition of absorption processes resulted in more variability in the prediction of the plasma profiles, irrespective of biopharmaceutics classification system (BCS) class. The reliability of literature permeability data was identified as a key issue in the accuracy of predicting oral drug absorption. Conclusion: For the four drugs studied, it appears that the forecasting accuracy of the PBPK models is related to the BCS class (BCS I > BCS II, BCS III > BCS IV). These results will need to be verified with additional drugs.

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If BCS class is predicted as I and II, mechanistic oral absorption modelling predictions may be straightforward, while class III and IV compounds may be more challenging.
“Thus, if the Biopharmaceutics Classification System (BCS) [27] class is predicted as I and II, mechanistic oral absorption modelling predictions may be straightforward, while class III and IV compounds may be more challenging [19, 28, 29].”
From Physiologically Based Pharmacokinetic Modelling for First-In-Human Predictions: An Updated Model Building Strategy Illustrated with Challenging Industry Case Studies (2019) · cites this paper as [29]

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Authors: Hansmann, S., Darwich, A., Margolskee, A., Aarons, L., & Dressman, J.
Affiliations: Goethe University Frankfurt (DE)
University of Manchester (GB)
Corresponding author: Dressman, Jennifer
ORCID: Darwich, Adam
Aarons, Leon
Dressman, Jennifer
Venue: Journal of Pharmacy and Pharmacology
Publisher: Oxford University Press (OUP)
Published: 2016-12-01
Volume: 68
Issue: 12
Pages: 1501-1515
ISSN: 0022-3573 (ISSN-L)
2042-7158
DOI: 10.1111/jphp.12618
OpenAlex: W2541098240
Cited by: 38
References: 67
Citations by year: 2026: 4 · 2025: 3 · 2024: 3 · 2023: 1 · 2022: 4 · 2021: 6 · 2020: 6 · 2019: 6 · 2018: 4 · 2017: 1
FWCI: 2.08
Type: journal article
Language: en
Open access: closed
Licence: academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
Locations: Journal of Pharmacy and Pharmacology (publishedVersion)
PubMed (publishedVersion)
Research Explorer (The University of Manchester) (submittedVersion)
Funders: Innovative Medicines Initiative (115369)
Topics: Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
Keywords: oral bioavailability, oral drug absorption, Biopharmaceutics Classification System, physiologically based pharmacokinetic modeling, parameter sensitivity analysis, bisoprolol, nifedipine, cimetidine, furosemide, prediction accuracy
MeSH terms: Administration, Oral, Animals, Biological Availability, Biopharmaceutics, Biotransformation, Cimetidine, Computer Simulation, Drug Compounding, Forecasting, Furosemide, Humans, Models, Biological, Nifedipine, Permeability, Reproducibility of Results, Bisoprolol, Administration, Intravenous, Gastrointestinal Absorption

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Forecasting oral absorption across biopharmaceutics classification system classes with physiologically based pharmacokinetic models

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