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  • Title: Anticonvulsant drugs differentially suppress individual ictal signs: a pharmacokinetic/pharmacodynamic analysis in the cortical stimulation model in the rat.
    Author: Jonker DM, van de Mheen C, Eilers PH, Kruk MR, Voskuyl RA, Danhof M.
    Journal: Behav Neurosci; 2003 Oct; 117(5):1076-85. PubMed ID: 14570556.
    Abstract:
    Antiepileptic drugs can suppress seizures completely, but they may also modify the appearance of drug-resistant seizures. In this study, the effects of three antiepileptic drugs on a seizure pattern were assessed by means of population pharmacokinetic/pharmacodynamic (PK/PD) modeling, yielding estimates of baseline response, EC50, and Hill slope. Lamotrigine did not affect eye closure, although it did suppress the other ictal signs in a concentration-dependent fashion. Midazolam suppressed forelimb clonus less potently than the other ictal signs; the same was observed for tiagabine with respect to eye closure. This study shows that ictal component analysis (ICA) in combination with PK/PD modeling may facilitate drug selection and dose optimization. The application of ICA is not restricted to a single seizure type or anticonvulsant drug and can be used to identify drug combinations that have a complementary action.
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