The Use of Systemically Absorbed Drugs to Explore An In Vitro Bioequivalence Approach For Comparing Non-Systemically...

Area of Science:

• Veterinary Pharmaceuticals
• Drug Bioequivalence
• Gastrointestinal Drug Delivery

Background:

• Evaluating bioequivalence (BE) for veterinary oral formulations acting locally in the gastrointestinal (GI) tract typically requires terminal clinical endpoint studies.
• There is a need for alternative methods to reduce animal testing in the assessment of these products.

Purpose of the Study:

• To explore a totality of evidence approach as an alternative to terminal clinical endpoint bioequivalence studies for veterinary locally acting GI products.
• To assess the utility of in vitro dissolution and product characteristics in predicting in vivo performance.

Main Methods:

• Three ivermectin plus praziquantel tablet formulations with distinct in vitro release profiles were manufactured.
• Plasma drug concentrations in Beagle dogs were used as biomarkers for in vivo dissolution.
• In vivo and in vitro bioequivalence predictions were compared across three dissolution media.

Main Results:

• Inconsistencies were observed between in vivo and in vitro product performance assessments for both active pharmaceutical ingredients (APIs).
• Differences in formulation and manufacturing were identified as potential reasons for the observed in vivo/in vitro discrepancies.

Conclusions:

• In vitro dissolution alone is insufficient to guarantee bioequivalence for veterinary locally acting GI products.
• A totality of evidence approach, integrating in vitro data with product composition and manufacturing details, can identify potential therapeutic inequivalence.
• This approach supports regulatory efforts to reduce, refine, and replace animal studies.