title: Pharmacodynamic interactions  between antiepileptic drugs:  preclinical data based on  isobolography.
abstract: 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.
authors.affiliation: Medical University of Lublin, Department of Pathophysiology, Lublin, Poland. czuczwarsj@yahoo.com
authors.forename: Stanislaw J
authors.initials: SJ
authors.lastname: Czuczwar
authors.forename: Jacek
authors.initials: J
authors.lastname: Kaplanski
authors.forename: Grazyna
authors.initials: G
authors.lastname: Swiderska-Dziewit
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Gergont
authors.forename: Slawomir
authors.initials: S
authors.lastname: Kroczka
authors.forename: Marek
authors.initials: M
authors.lastname: Kacinski
mesh_terms: 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
chemical_list: D000927:Anticonvulsants