Related Experiment Video
Updated: Jul 20, 2026

A Novel In vitro Model for Studying the Interactions Between Human Whole Blood and Endothelium
Published on: November 21, 2014
Integrating In Vitro, Modeling, and In Vivo Approaches to Investigate Warfarin Bioequivalence
1Office of Generic Drugs, US Food and Drug Administration, Silver Spring, Maryland, USA.
Abstract:
We demonstrate the use of modeling and simulation to investigate bioequivalence (BE) concerns raised about generic warfarin products. To test the hypothesis that the loss of isopropyl alcohol and slow dissolution in acidic pH has significant impact on the pharmacokinetics of warfarin sodium tablets, we conducted physiologically based pharmacokinetic absorption modeling and simulation using formulation factors or in vitro dissolution profiles as input parameters. Sensitivity analyses indicated that warfarin pharmacokinetics was not sensitive to solubility, particle size, density, or dissolution rate in pH 4.5, but was affected by dissolution rate in pH 6.8 and potency. Virtual BE studies suggested that stressed warfarin sodium tablets with slow dissolution rate in pH 4.5 but having similar dissolution rate in pH 6.8 would be bioequivalent to the unstressed warfarin sodium tablets. A four-way, crossover, single-dose BE study in healthy subjects was conducted to test the same hypothesis and confirmed the simulation conclusion.
Related Concept Videos
Methods for Studying Drug Absorption: In vitro
The diffusion cell method uses a two-compartment cell, including a donor compartment with the drug solution, which simulates the environment where the drug is applied, and a receptor compartment with a buffer solution, which simulates the environment...
Equivalence: In Vitro and In Vivo Bioequivalence
Bioequivalence studies: Biowaivers
In Vitro Drug Dissolution: Compendial Testing Models I
In Vitro Drug Dissolution: Compendial Testing Models II
Drug Product Performance: In Vitro–In Vivo Correlation

