Table 2. Type I isobolographic analysis of interactions for non-parallel 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 | L-ED50 add (mg/kg) | n add | U-ED50 add (mg/kg) | n add | I-index | Types of interaction |
---|---|---|---|---|---|---|---|---|
GBP + LCM | 19.20 ± 5.78 | 8 | 29.33 ± 10.56 | 44 | 47.35 ± 11.56 | 44 | 0.65 | additivity |
LEV + LCM | 1.73 ± 0.26 * | 24 | 7.26 ± 3.36 | 44 | 11.73 ± 3.90 | 44 | 0.24 | synergy |
RTG + LCM | 12.12 ± 1.81 | 24 | 12.45 ± 4.22 | 52 | 21.15 ± 4.82 | 52 | 0.97 | additivity |
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)
L-ED50 add value calculated from the equation for the lower line of additivity; U-ED50 add value calculated from the equation for the upper line of additivity; I-index–interaction index as a ratio of ED50 exp and L-ED50 add values
*P<0.05 vs. the respective ED50 add value.