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. 2020 Jun 1;15(6):e0234070. doi: 10.1371/journal.pone.0234070

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, 8688]. 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.