Anticonvulsant drugs differentially suppress individual ictal signs: a pharmacokinetic/pharmacodynamic analysis in the cortical stimulation model in the rat
Publication Type:Journal Article
Source:Behav Neurosci, Volume 117, Number 5, p.1076-85 (2003)
DOI Name (links to online publication)10.1037/0735-7044.117.5.10762003-08567-020 [pii]
Keywords:Animals; Anticonvulsants/*pharmacokinetics/pharmacology/therapeutic use; Cerebral Cortex/*drug effects/*metabolism; *Disease Models; Animal; Dose-Response Relationship; Drug; Electric Stimulation; Male; Rats; Rats; Wistar; Seizures/drug therapy/*metabolis
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.