Interactions between tiagabine and conventional antiepileptic drugs in the rat model of complex partial seizures.
This study evaluated the interactions between tiagabine (TGB) and three conventional antiepileptic drugs (AEDs): valproate (VPA), carbamazepine (CBZ), and phenobarbital (PB) in amygdala-kindled rats, a reliable model of complex partial seizures in humans. Isobolographic analysis of interactions revealed that TGB interacted additively with all tested conventional AEDs for the fixed-ratio combinations of 1:3, 1:1, and 3:1. Evaluation of pharmacokinetic interactions between AEDs revealed that the observed additivity was pharmacodynamic in nature. TGB did not affect the plasma and brain concentrations of VPA, CBZ and PB. Similarly, none of the studied conventional AEDs changed the plasma or brain levels of TGB. Also, TGB, VPA, CBZ, and PB administered alone (at their median effective doses) and in combinations at the fixed-ratio of 1:1 did not impair motor performance evaluated in the chimney test. In conclusion, additivity between TGB and conventional AEDs in amygdala-kindled rats and lack of bidirectional pharmacokinetic interactions suggest that TGB appears to be a valuable drug for an add-on therapy of refractory complex partial seizures in humans.
Borowicz
K K
KK
Department of Pathophysiology, Medical University, Lublin, Poland. kinga.borowicz@am.lublin.pl
Zadrozniak
M
M
Luszczki
J J
JJ
Czuczwar
S J
SJ
D000679:Amygdala / Q000503:physiopathology; D000704:Analysis of Variance; D000818:Animals; D000927:Anticonvulsants / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004828:Epilepsies, Partial / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D008297:Male; D009557:Nipecotic Acids / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index; D000078308:Tiagabine
D000927:Anticonvulsants; D009557:Nipecotic Acids; D000078308:Tiagabine