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Predicting fraction dose absorbed in humans using a macroscopic mass balance approach
P J Sinko1, G D Leesman, G L Amidon
1College of Pharmacy, University of Michigan, Ann Arbor 48109-1065.
Pharmaceutical Research
|August 1, 1991
Summary
A new macroscopic mass balance approach (MMBA) estimates drug absorption in humans using fundamental mass transfer theory. This model, incorporating permeability and solubility, accurately predicts fraction dose absorbed for various drugs, including amoxicillin.
Area of Science:
- Pharmacokinetics
- Biopharmaceutics
- Physiology
Background:
- Estimating oral drug absorption in humans is crucial for effective dosing.
- Existing models often lack a strong theoretical basis or fail to account for solubility limitations.
- A unified theoretical framework is needed to predict drug absorption across different scenarios.
Purpose of the Study:
- To develop a theoretically grounded model for estimating the fraction of a drug dose absorbed in humans.
- To incorporate membrane permeability and drug solubility into a macroscopic mass balance approach (MMBA).
- To demonstrate the MMBA's applicability to both passive and non-passive drug absorption, including solubility-limited cases.
Main Methods:
- Developed a macroscopic mass balance approach (MMBA) based on fundamental mass transfer theory.
- Incorporated parameters such as intestinal length, radius, wall permeability, and axial fluid velocity.
- Considered three theoretical cases based on initial concentration and solubility.
- Applied the MMBA to amoxicillin, using in situ/in vitro data and comparing predictions with human pharmacokinetic data.
Main Results:
- The MMBA provides a theoretical framework for estimating fraction dose absorbed, unifying existing empirical correlations as special cases.
- The model accurately predicted amoxicillin absorption across different doses, considering its solubility and non-passive absorption mechanism.
- MMBA predictions showed good agreement with human pharmacokinetic data from literature.
Conclusions:
- The macroscopic mass balance approach (MMBA) is a fundamental, theoretically sound model for predicting human drug absorption.
- MMBA integrates key physiological and physicochemical parameters, offering a versatile tool for biopharmaceutical research.
- This approach enhances the understanding of drug absorption, particularly for drugs with complex absorption mechanisms or solubility constraints.