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

Abstract

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.