Beneficial combination of lacosamide with retigabine in experimental animals: An isobolographic analysis
PBN-AR
Instytucja
Instytut Medycyny Wsi im. Witolda Chodźki
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Główny język publikacji
Czasopismo
PHARMACOLOGY (20pkt w roku publikacji)
ISSN
0031-7012
EISSN
Wydawca
KARGER
DOI
URL
Rok publikacji
2017
Numer zeszytu
1-2
Strony od-do
22-28
Numer tomu
101
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Streszczenia
Język
angielski
Treść
Background/aim: To isobolographically determine the types of interactions that occur between retigabine and lacosamide (LCM; two third-generation antiepileptic drugs) with respect to their anticonvulsant activity and acute adverse effects (sedation) in the maximal electroshock-induced seizures (MES) and chimney test (motor performance) in adult male Swiss mice. Methods: Type I isobolographic analysis for nonparallel dose-response effects for the combination of retigabine with LCM (at the fixed-ratio of 1:1) in both the MES and chimney test in mice was performed. Brain concentrations of retigabine and LCM were measured by high-pressure liquid chromatography (HPLC) to characterize any pharmacokinetic interactions occurring when combining these drugs. Results: Linear regression analysis revealed that retigabine had its dose-response effect line nonparallel to that of LCM in both the MES and chimney tests. The type I isobolographic analysis illustrated that retigabine combined with LCM (fixed-ratio of 1:1) exerted an additive interaction in the mouse MES model and sub-additivity (antagonism) in the chimney test. With HPLC, retigabine and LCM did not mutually change their total brain concentrations, thereby confirming the pharmacodynamic nature of the interaction. Conclusion: LCM combined with retigabine possesses a beneficial preclinical profile (benefit index ranged from 2.07 to 2.50) and this 2-drug combination is worth recommending as treatment plan to patients with pharmacoresistant epilepsy.
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System-identifier
PX-5c6d500bd5de53283d9d894b
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