Predicting oral drug absorption and hepatobiliary clearance: Human intestinal and hepatic in vitro cell models

Richard A Fearn1, Barry H Hirst

  • 1Institute for Cell and Molecular Biosciences, University of Newcastle, Medical School, Newcastle upon Tyne NE2 4HH, UK.

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Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance

Drug transporters are critical in drug absorption, distribution, and excretion processes. They should be included in physiological-based pharmacokinetic (PBPK) models, which help predict human drug disposition. However, predicting this is challenging during drug development, especially when liver transport is involved. However, with a realistic representation of body transport processes, an accurate model may be possible.
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Hepatic Drug Clearance: Role of Transporters

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In situ experiments, such as the Doluisio method and Single-Pass Perfusion technique, provide critical insights into drug uptake by simulating in vivo conditions for drug absorption.
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Modified-Release Drug Delivery Systems: Bioavailability

Modified-release (MR) dosage forms are designed to extend drug release over time, thereby maintaining stable plasma concentrations and reducing dosing frequency. However, their bioavailability is typically below 100% due to incomplete drug release and presystemic metabolism, and limitations in drug permeability across the gastrointestinal epithelium, all of which can restrict the fraction of the drug reaching systemic circulation. Consequently, studying the in vivo bioavailability of MR...
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Drug Absorption: Factors Affecting GI Absorption

The process of oral drug absorption can be influenced by several factors. Weakly acidic drugs tend to be absorbed more readily from the stomach due to their nonionized state. However, absorption may be less efficient in the upper intestine, where drugs are often ionized. Interestingly, despite the stomach's apparent advantage for drug absorption, its mucous layer can hinder diffusion. Its surface area is also smaller than the intestine's, which can further slow down the absorption rate.
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