Log-probit accompanied with Tallarida and Chou-Talalay-Martin methods in an isobolographic analysis of interactions between two antiseizure medications - a comparative study.

BACKGROUND

The isobolographic analysis is a gold standard in the assessment of interactions between drugs in experimental studies. Although some isobolographic approaches are available, the most popular methods to characterize drug-drug interactions are the log-probit method accompanied with statistical analysis of interactions (by Tallarida) and the method based on mass-action law using CompuSyn software (elaborated by Chou-Talalay-Martin). The aim of this study was to compare the results from these two isobolographic approaches.

METHODS

Two isobolographic methods (log-probit associated with Tallarida statistics and Chou-Talalay-Martin) were applied to analyze the interaction between two antiseizure medications - clonazepam and lamotrigine in the mouse maximal electroshock-induced seizure model.

RESULTS

Both isobolographic approaches confirmed that the combination of clonazepam with lamotrigine produced synergistic interaction and allowed for detailed characteristics of the interaction at various effect levels for the two-drug mixture. Calculation of the combination index values (at various effect levels) confirmed that synergy slightly decreased when the antiseizure effect increased (combination index values increased from 0.44 for 16% to 0.65 for 84%).

CONCLUSIONS

The log-probit method with statistical analysis of data (by Tallarida) was more subtle and precise in the assessment of the synergistic interaction, whereas the isobolographic analysis by Chou-Talalay-Martin offered more automatic options facilitating visualization of the interaction.