[Validation of in situ single pass perfusion model based on P-gp]

Area of Science:

• Pharmacology
• Gastroenterology
• Drug Delivery Systems

Background:

• The P-glycoprotein (P-gp) efflux transporter plays a crucial role in drug absorption and distribution.
• Validating in situ intestinal models is essential for studying P-gp mediated drug transport.
• The rat intestinal single-pass perfusion model offers a controlled environment for such investigations.

Purpose of the Study:

• To validate an in situ rat intestinal single-pass perfusion model for P-gp research.
• To assess the integrity of the intestinal epithelium using phenol red.
• To evaluate the model's capacity to study P-gp efflux transporter activity with digoxin and verapamil.

Main Methods:

• Phenol red perfusion was conducted to assess intestinal epithelial integrity and water flux.
• High-performance liquid chromatography (HPLC) was used to quantify phenol red levels.
• Digoxin absorption was measured in rat ileum segments with varying verapamil concentrations.

Main Results:

• Phenol red perfusion confirmed normal intestinal epithelial structure and integrity.
• Digoxin absorption in the rat ileum was observed, with increased permeability in the presence of verapamil.
• Effective permeability coefficients (Peff) for digoxin significantly increased with verapamil concentrations (P<0.05).

Conclusions:

• The in situ rat intestinal single-pass perfusion model is validated for P-gp research.
• The model effectively demonstrates P-gp mediated efflux transporter activity.
• This model can be utilized for further investigations into P-gp substrate and inhibitor interactions.