OTHER / RESEARCH PAPER
ISOBOLOGRAPHIC ASSESSMENT OF INTERACTIONS BETWEEN RETIGABINE AND PHENYTOIN IN THE MOUSE MAXIMAL ELECTROSHOCK-INDUCED SEIZURE MODEL AND CHIMNEY TEST
1
University of California Davis School of Medicine, Sacramento, United States of America
2
Institute of Rural Health, Isobolographic Analysis Laboratory, Lublin, Poland
3
Medical University of Lublin, Department of Pathophysiology, Poland
4
Institute of Rural Health, Centre of Public Health and Health Promotion, Lublin, Poland
5
The Jan Kochanowski University in Kielce, Faculty of Medicine and Health Sciences, Poland
6
Medical University of Lublin, Department of Otolaryngology, Poland
Submission date: 2016-09-05
Final revision date: 2016-10-12
Acceptance date: 2016-10-17
Publication date: 2016-12-13
Health Prob Civil. 2016;10(4):54-59
KEYWORDS
TOPICS
ABSTRACT
Background. Search for beneficial combinations of antiepileptic drugs (AEDs) that can be used in patients with pharmacoresistant epilepsy, is still conducted both empirically and rationally, based on molecular mechanisms of AEDs’ action. This study was aimed at characterizing the interaction profiles for the combination of two AEDs (i.e., retigabine [RTG] and phenytoin [PHT]) in the maximal electroshock-induced seizures (MES) and chimney test (motor performance) in adult male albino Swiss mice.
Material and methods. Type I isobolographic analysis was used to determine interactions for the combination of RTG with PHT (at three fixed-ratios of 1:3, 1:1 and 3:1) with respect to its anticonvulsant and acute neurotoxic effects in the MES and chimney tests, respectively. Total brain concentrations of RTG and PHT were estimated to exclude any pharmacokinetic interaction between AEDs.
Results. The combination of RTG with PHT at the fixed-ratios of 1:3, 1:1 and 3:1 produced additive interactions in both, the MES and chimney tests. RTG and PHT did not affect each other their total brain concentrations in mice, confirming pharmacodynamic interaction between the investigated drugs. Conclusions. The combination of RTG with PHT was neutral
suggesting that this two-drug combination might occur favorable in some patients with refractory epilepsy.
Material and methods. Type I isobolographic analysis was used to determine interactions for the combination of RTG with PHT (at three fixed-ratios of 1:3, 1:1 and 3:1) with respect to its anticonvulsant and acute neurotoxic effects in the MES and chimney tests, respectively. Total brain concentrations of RTG and PHT were estimated to exclude any pharmacokinetic interaction between AEDs.
Results. The combination of RTG with PHT at the fixed-ratios of 1:3, 1:1 and 3:1 produced additive interactions in both, the MES and chimney tests. RTG and PHT did not affect each other their total brain concentrations in mice, confirming pharmacodynamic interaction between the investigated drugs. Conclusions. The combination of RTG with PHT was neutral
suggesting that this two-drug combination might occur favorable in some patients with refractory epilepsy.
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| eISSN: | 2354-0265 |
| ISSN: | 2353-6942 |
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