presentation/249 1st BioSim Conference - Presentation

1st BioSim Conference


A simple physiological-pharmacokinetic model to simulate bioequivalence trials

Author: Marival Bermejo, Universidad de Valencia.

Names and affiliation of other authors:
1. Nalda Molina, Ricardo: Universidad de Valencia
2. Bermejo, Marival: Universidad de Valencia
3. Casabó ,Vicente: Universidad de Valencia

Oral or poster: Poster

The analyte to be evaluated in bioequivalence trials is still today a controversial issue. The objective of this work is to use computer simulation approach to solve gaps in regulatory guidances regarding bioavailability (BA) and bioequivalence assessment (BE), especially in drugs undergoing metabolic clearance. The conclusions of the present work can lead to new recommendations for analyte selection in the BE trials.
Simulated BE studies were performed using NONMEM. A semi-physiological model was used, including dissolution compartment, degradation in lumen, operative absorption time and hepatic first-pass effect. Parent drug and metabolite were simulated for both reference and test.
To simulate non-bioequivalent formulations, different scenarios were performed by varying the values of dissolution constant in lumen or the degradation in lumen or the operation absorption time or a combination of all three.
On top of that, the hepatic clearance and its inter-individual variability were also varied to detect any dependency in the best analyte to choose (parent drug or metabolite) and the hepatic clearance.
The results of all the simulations will be presented as percentage of success for the metabolite and the parent drug. The scenarios will be split on 2 groups, with test and reference being truly bioequivalent or when they were not. Finally, either metabolite or parent drug would be selected depending on the results of the simulation.

1st BioSim Conference. October 6th to October 8th, 2005. Palma de Mallorca, Spain.