<abstract xmlns="http://www.w3.org/1999/xhtml"><sec id="j_joepi-2016-0016_s_001"><h3>Introduction</h3><p>Patients with pharmacoresistant epilepsy are usually treated with two or more antiepileptic drugs (AEDs). The search for therapeutically efficacious AED combinations is still a challenging issue for clinicians and epileptologists throughout the world.</p></sec><sec id="j_joepi-2016-0016_s_002"><h3>Aim</h3><p>To determine the interaction profile for the combination of retigabine (RTG) and oxcarbazepine (OXC) in both, the model of tonic-clonic seizures, the maximal electroshock (MES)-induced seizure model and chimney test (motor performance) in adult male albino Swiss mice.</p></sec><sec id="j_joepi-2016-0016_s_003"><h3>Methods</h3><p>Isobolographic analysis (type I) was applied to characterize interactions for the combination of RTG with OXC with respect to its anticonvulsant and acute side (neurotoxic) effects, as determined in the MES and chimney tests, respectively.</p></sec><sec id="j_joepi-2016-0016_s_004"><h3>Results</h3><p>The combination of RTG with OXC at the fixed-ratios of 1:3, 1:1 and 3:1 produced additive interactions in the MES test in mice. Similarly, the combination of RTG with OXC at the fixed-ratio of 1:1 produced additive interaction with a tendency towards sub-additivity in the chimney test in mice. Measurement of total brain concentrations of both AEDs revealed that RTG did not affect total brain concentrations of OXC and inversely, OXC had no impact on RTG’s total brain concentrations, confirming pharmacodynamic interaction between the drugs.</p></sec><sec id="j_joepi-2016-0016_s_005"><h3>Conclusions</h3><p>The additive pharmacodynamic interactions in both the MES and chimney tests in mice were observed for the combination of RTG with OXC.</p></sec></abstract>

IntroductionPatients with pharmacoresistant epilepsy are usually treated with two or more antiepileptic drugs (AEDs). The search for therapeutically efficacious AED combinations is still a challenging issue for clinicians and epileptologists throughout the world.AimTo determine the interaction profile for the combination of retigabine (RTG) and oxcarbazepine (OXC) in both, the model of tonic-clonic seizures, the maximal electroshock (MES)-induced seizure model and chimney test (motor performance) in adult male albino Swiss mice.MethodsIsobolographic analysis (type I) was applied to characterize interactions for the combination of RTG with OXC with respect to its anticonvulsant and acute side (neurotoxic) effects, as determined in the MES and chimney tests, respectively.ResultsThe combination of RTG with OXC at the fixed-ratios of 1:3, 1:1 and 3:1 produced additive interactions in the MES test in mice. Similarly, the combination of RTG with OXC at the fixed-ratio of 1:1 produced additive interaction with a tendency towards sub-additivity in the chimney test in mice. Measurement of total brain concentrations of both AEDs revealed that RTG did not affect total brain concentrations of OXC and inversely, OXC had no impact on RTG’s total brain concentrations, confirming pharmacodynamic interaction between the drugs.ConclusionsThe additive pharmacodynamic interactions in both the MES and chimney tests in mice were observed for the combination of RTG with OXC.

Additive interactions between retigabine and oxcarbazepine in the chimney test and the model of generalized tonic-clonic seizures in mice

Journal of Epileptology

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

IntroductionPatients with pharmacoresistant epilepsy are usually treated with two or more antiepileptic drugs (AEDs). The search for therapeutically...

Additive interactions between retigabine and oxcarbazepine in the chimney test and the model of generalized tonic-clonic seizures in mice

Published Online: Dec 22, 2016

Page range: 87 - 94

Received: Nov 10, 2016

Accepted: Dec 19, 2016

DOI: https://doi.org/10.21307/joepi-2016-0016

Keywords
anticonvulsant, drug interactions, electroshock

© 2016 Mirosław Zagaja et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Additive interactions between retigabine and oxcarbazepine in the chimney test and the model of generalized tonic-clonic seizures in mice

Published Online: Dec 22, 2016

Page range: 87 - 94

Received: Nov 10, 2016

Accepted: Dec 19, 2016

DOI: https://doi.org/10.21307/joepi-2016-0016

Keywordsanticonvulsant, drug interactions, electroshock

© 2016 Mirosław Zagaja et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Keywords
anticonvulsant, drug interactions, electroshock