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Updated: May 13, 2026
08:59
An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
Published on: December 3, 2020
Predicting intestinal absorption of raltegravir using a population-based ADME simulation.
Darren M Moss1, Marco Siccardi, David J Back
1Molecular and Biochemical Parasitology Group, Liverpool School of Tropical Medicine, Liverpool, UK. darren.moss@liverpool.ac.uk
The Journal of Antimicrobial Chemotherapy
|March 22, 2013
Summary
This study developed a model to predict how gastrointestinal pH and magnesium affect raltegravir pharmacokinetics (PK). Higher pH increased absorption, while magnesium reduced raltegravir exposure, impacting drug effectiveness.
Area of Science:
- Pharmacokinetics
- Drug metabolism and disposition
- Computational modeling
Background:
- Raltegravir pharmacokinetics (PK) exhibit significant variability.
- Gastrointestinal factors like pH and co-administered substances (e.g., magnesium) can alter raltegravir absorption.
- Understanding these interactions is crucial for optimizing raltegravir therapy.
Purpose of the Study:
- To develop a population-based absorption, distribution, metabolism, and excretion (ADME) model for raltegravir.
- To investigate the impact of gastrointestinal pH on raltegravir PK.
- To assess the effect of ingested magnesium on raltegravir PK.
Main Methods:
- Utilized in vitro data and standard methods to describe raltegravir disposition.
- Simulated raltegravir PK (400 mg single dose) in a virtual population over 12 hours.
- Developed a population-based ADME model for in vitro-in vivo extrapolation.
Main Results:
- Simulated PK correlated well with clinical trial data (mean deviation <20%).
- Increased gastrointestinal pH and transit time positively correlated with raltegravir absorption (P<0.001).
- Magnesium ingestion significantly reduced raltegravir exposure, with mean C(trough) decreased by 32% (P<0.001).
Conclusions:
- The developed in vitro-in vivo extrapolation model accurately predicted raltegravir PK.
- Gastrointestinal pH and magnesium significantly influence raltegravir absorption.
- This modeling system can aid in evaluating other drugs, including novel HIV integrase inhibitors.
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