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An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
Published on: December 3, 2020
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Forecasting oral absorption across biopharmaceutics classification system classes with physiologically based
Simone Hansmann1, Adam Darwich2, Alison Margolskee2
1Institute of Pharmaceutical Technology, Goethe University Frankfurt am Main, Frankfurt am Main, Germany.
The Journal of Pharmacy and Pharmacology
|October 27, 2016
Summary
Physiologically based pharmacokinetic (PBPK) models accurately predict oral drug bioavailability. Prediction accuracy is influenced by the Biopharmaceutics Classification System (BCS) class, with better results for BCS I and III drugs.
Area of Science:
- Pharmacokinetics and Drug Metabolism
- Computational Modeling in Pharmacology
Background:
- Physiologically based pharmacokinetic (PBPK) models are crucial for predicting drug behavior in the body.
- Understanding oral bioavailability is key for effective drug development and dosage formulation.
Purpose of the Study:
- To assess the predictive accuracy of PBPK models for oral bioavailability using a priori data.
- To investigate the impact of the Biopharmaceutics Classification System (BCS) on PBPK simulation success.
Main Methods:
- Utilized Simcyp Simulator, GastroPlus™, and GI-Sim software.
- Selected drugs with Biowaiver monographs (bisoprolol, nifedipine, cimetidine, furosemide) representing BCS classes I-IV.
- Evaluated simulation accuracy using Average Fold Error (AFE) and Absolute Average Fold Error (AAFE).
Main Results:
- PBPK models accurately predicted intravenous plasma concentration-time profiles (AAFE < 3).
- Incorporating absorption processes increased prediction variability across all BCS classes.
- The accuracy of literature-reported permeability data significantly impacts oral absorption predictions.
Conclusions:
- PBPK model forecasting accuracy for oral bioavailability appears correlated with BCS class (BCS I > II, III > IV).
- Further studies with additional compounds are needed to validate these findings.
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