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Intestinal permeability enhancement: efficacy, acute local toxicity, and reversibility
E S Swenson1, W B Milisen, W Curatolo
1Pharmaceutical R&D Department, Central Research Division, Pfizer, INC 06340.
Pharmaceutical Research
|August 1, 1994
Summary
Surfactants like SDS and NP-POE enhance drug absorption by increasing intestinal permeability, but can cause damage. This damage and enhanced permeability are reversible, with rapid repair observed after enhancer removal.
Area of Science:
- Pharmacology
- Gastroenterology
- Drug Delivery
Background:
- Intestinal permeability is crucial for drug absorption.
- Understanding enhancers is key for improving oral drug bioavailability.
- Assessing safety alongside efficacy is vital for drug development.
Purpose of the Study:
- To evaluate the impact of various surfactants on intestinal drug absorption.
- To investigate the relationship between permeability enhancement and intestinal wall damage.
- To determine the reversibility of enhancer-induced effects.
Main Methods:
- Rat intestinal perfusion model using phenol red as a model drug.
- Measurement of absorption rate constant (KA) and plasma drug concentration.
- Assay of biochemical markers (LDH, lipid phosphate) and histological evaluation for intestinal damage.
Main Results:
- Sodium dodecyl sulfate (SDS) and nonylphenoxypolyoxyethylene (NP-POE)-10.5 were potent permeability enhancers.
- Sodium taurodeoxycholate (TDC) was more effective than sodium taurocholate (TC).
- Enhanced permeability and intestinal damage were correlated and rapidly reversible within 1-3 hours.
Conclusions:
- Permeability enhancement by surfactants is closely linked to intestinal wall damage.
- Surfactant-induced acute intestinal damage is rapidly repaired.
- These findings have implications for designing safer drug delivery systems.