Beneficial combination of lacosamide with retigabine in experimental animals: An isobolographic analysis
PBN-AR
Instytucja
Instytut Medycyny Wsi im. Witolda Chodźki
Informacje podstawowe
Główny język publikacji
angielski
Czasopismo
PHARMACOLOGY (20pkt w roku publikacji)
ISSN
0031-7012
EISSN
Wydawca
KARGER
DOI
URL
Rok publikacji
2018
Numer zeszytu
Strony od-do
22-28
Numer tomu
101
Link do pełnego tekstu
Identyfikator DOI
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Słowa kluczowe
angielski
Antiepileptic drugs
Drug interactions
Isobolographic analysis
Lacosamide
Maximal electroshock seizure test
Retigabine
Streszczenia
Język
angielski
Treść
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.
Inne
System-identifier
PX-5c73e06ad5de11c176d62732
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