Pharmacodynamic and/or pharmacokinetic characteristics of interactions between loreclezole and four conventional antiepileptic drugs in pentylenetetrazole-induced seizures in mice: An isobolographic analysis

In conclusion, BI, which is a measure of the margin of safety and tolerability of drugs in combination and comprises anticonvulsant and neurotoxic measures, was favorable for only one combination (LCZ and ETS at a fixed ratio of 1:3) with a value of 1.39. In contrast, LCZ and CZP constitute an unfavorable combination (BI = 0.61-1.01). The combinations of LCZ with PB or VPA do not offer any advantage as assessed by the parameters (BI range: 0.75-0.91) used in this study. However, these conclusions are confounded by the fact that LCZ is associated with significant pharmacokinetic interactions.