Table 1. Type I isobolographic analysis of interactions for collateral dose-response relationship lines between antiepileptic drugs (at the fixed drug dose ratio of 1:1) in the 6-Hz corneal stimulation-induced seizure model in mice.
Drug combination | ED50 exp (mg/kg) | n exp | ED50 add (mg/kg) | n add | I-index | Types of interaction |
---|---|---|---|---|---|---|
PGB + LCM | 8.17 ± 2.40 * | 24 | 18.11 ± 4.42 | 36 | 0.45 | synergy |
GBP + LEV | 15.06 ± 5.03 ** | 16 | 43.27 ± 6.47 | 44 | 0.35 | synergy |
PGB + LEV | 7.20 ± 2.39 ** | 16 | 23.04 ± 4.78 | 36 | 0.31 | synergy |
GBP + RTG | 12.62 ± 3.81 *** | 8 | 50.57 ± 7.30 | 52 | 0.25 | synergy |
LEV + RTG | 3.24 ± 0.55 *** | 16 | 21.73 ± 2.99 | 52 | 0.15 | synergy |
PGB + GBP | 44.36 ± 5.51 | 16 | 51.88 ± 9.09 | 36 | 0.86 | additivity |
PGB + RTG | 12.41 ± 3.32 ** | 16 | 30.34 ± 5.61 | 44 | 0.41 | synergy |
The experimentally-derived median effective doses (ED50 exp values in mg/kg ± S.E.M.) for two-drug mixtures were statistically compared to their respective theoretically calculated additive median effective doses (ED50 add values in mg/kg ± S.E.M.) by the use of unpaired Student’s t-test with Welch’s correction as recommended elsewhere [60, 86–88]. n exp−total number of animals used at those doses whose expected antiseizure effects ranged between 16% and 84% (i.e., 4 and 6 probits) for the experimental mixture; n add−total number of animals calculated for the additive mixture of the drugs examined (n add = n_antiepileptic drug_1 + n_antiepileptic drug_2−4); I-index–interaction index as a ratio of ED50 exp and ED50 add values
*P<0.05
**P<0.01
***P<0.001 vs. the respective ED50 add value.