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A modified two-portion absorption model to describe double-peak absorption profiles of ranitidine
Ophelia Q P Yin1, Brian Tomlinson, Albert H L Chow
1School of Pharmacy, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
Clinical Pharmacokinetics
|January 23, 2003
Summary
A new modified two-portion absorption model effectively describes ranitidine
Area of Science:
- Pharmacokinetics
- Drug Absorption Modeling
- Biopharmaceutics
Background:
- Conventional pharmacokinetic models struggle with drugs exhibiting double peaks.
- Understanding double-peak phenomena is crucial for accurate drug dosing and efficacy.
Purpose of the Study:
- To propose and validate a modified two-portion absorption model for drugs with double-peak concentration-time profiles.
- To describe the double-peak concentration-time curve of ranitidine using physiological and biopharmaceutical principles.
Main Methods:
- A modified two-portion absorption model was developed, incorporating a gut compartment for sequential absorption.
- Model validation included structural identifiability, parameter estimability, and fitting to ranitidine oral data from subjects with double and single peaks.
- Initial parameter estimates were derived from previous intravenous data.
Main Results:
- The model demonstrated excellent goodness-of-fit for both double-peak and single-peak ranitidine concentration-time curves.
- Simulation studies confirmed good accuracy and precision of the fitted model parameters.
- The model accurately characterized the absorption phase and estimated pharmacokinetic parameters.
Conclusions:
- The modified two-portion absorption model provides a robust approach for characterizing drug absorption with double peaks.
- This model enhances the understanding of complex pharmacokinetic profiles for improved therapeutic outcomes.