Pharmacodynamic interactions  between antiepileptic drugs:  preclinical data based on  isobolography.
BACKGROUND
At least 20 - 30% of epileptic patients do not sufficiently respond to monotherapy. Some of them can benefit from drug combinations; hence, animal data may provide some useful novel clues for rational polytherapy.


OBJECTIVE
To review combinations of antiepileptic drugs, evaluated with the help of isobolographic analysis, in terms of their efficacy and adverse effects.


METHODS
A literature search, on the basis of experimental studies, with no time limit was carried out.


CONCLUSIONS
Preclinical data indicate that a synergy occurred for the combinations of valproate + phenytoin, valproate + ethosuximide, lamotrigine + valproate, gabapentin + valproate, gabapentin + carbamazepine, topiramate + carbamazepine, topiramate + valproate, topiramate + oxcarbazepine, levetiracetam + topiramate, levetiracetam + oxcarbazepine, oxcarbazepine + gabapentin, tiagabine + gabapentin and lamotrigine + topiramate. On the other hand, lamotrigine combined with carbamazepine or oxcarbazepine resulted in a clear-cut antagonism. Interestingly, a combination of oxcarbazepine + clonazepam produced variable responses, including synergy, additivity or antagonism, depending on the dose ratio of these drugs. In no case did pharmacokinetic factors contribute to the final analysis of the effects of drug combinations. Pharmacokinetic factors can contribute to the final effect of drug combinations,such as when stiripentol is added to valproate, or clobazam is added to valproate. It may be concluded that the rational treatment of drug-resistant epilepsy needs to consider the results of preclinical studies.
Czuczwar
Stanislaw J
SJ
Medical University of Lublin, Department of Pathophysiology, Lublin, Poland. czuczwarsj@yahoo.com
Kaplanski
Jacek
J
Swiderska-Dziewit
Grazyna
G
Gergont
Aleksandra
A
Kroczka
Slawomir
S
Kacinski
Marek
M
D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004347:Drug Interactions; D004351:Drug Resistance; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000188:drug therapy*; D006801:Humans
D000927:Anticonvulsants