A pharmacokinetic model for multiple sites discontinuous gastrointestinal absorption

Area of Science:

• Pharmacokinetics
• Mathematical Modeling
• Drug Absorption

Background:

• Oral drug absorption is often discontinuous, occurring at multiple intestinal sites.
• Existing models may not fully capture complex absorption profiles.
• Understanding site-specific absorption is crucial for optimizing drug efficacy.

Purpose of the Study:

• To develop a general pharmacokinetic model for discontinuous drug absorption from multiple successive intestinal sites.
• To analytically solve the model to determine drug concentration, absorption contribution, area under the curve (AUC), and bioavailability.
• To provide a tool for characterizing individual absorption sites.

Main Methods:

• Developed a pharmacokinetic model incorporating discontinuous absorption from 'n' successive intestinal sites with intervening non-absorbing segments.
• Utilized Laplace transforms to derive analytical expressions for drug amounts, plasma concentration, AUC, and bioavailability.
• Applied Heaviside's theorem for n=2 sites and Bromwich's theorem for n>=3 sites.

Main Results:

• The model successfully simulates drug absorption, demonstrating the efficacy of individual absorption sites.
• A specific case for n=2 sites was validated using ranitidine data from the literature.
• Real-world data with three absorption peaks were accurately fitted using the n=3 site model.

Conclusions:

• The proposed general pharmacokinetic model effectively characterizes discontinuous oral absorption.
• This model serves as a valuable tool for quantifying the contribution of each absorption site.
• It enables accurate estimation of area under the curve and bioavailability for drugs with complex absorption patterns.