Antiepileptic drugs protein binding

Leone, A.M. et al. (2007) Evaluation of felbamate and other antiepileptic drug toxicity potential based on hepatic protein covalent binding and gene expression. Chemical Research in Toxicology, 20 (4), 600-608. 

Cloyd, J.C., Fischer, J.H., Kriel, R.L., and Kraus, D.M. (1993) Valproic acid pharmacokinetics in children. IV. Effects of age and antiepileptic drugs on protein binding and intrinsic clearance. Clin Pharmacol Ther 53 22-29. 

Lynch BA et al The synaptic vesicle protein SV2A is the binding site for the antiepileptic drug levetiracetam. Proc Natl Acad Sci U S A 2004 101 9861. [PMID 15210974]... 

Valproic add modulates the action of various other common antiepileptic drugs. It inhibits the nonrenal clearance of phenobarbital, resulting in elevated phenobarbital levels. It competes -with phenytoin for protein-binding sites. The free phenytoin concentration remains approximately the same, but the total phenytoin in the plasma decreases. Because the free phenytoin concentration remains unchanged, the pharmacological effect is retained. Other common antiepileptic drugs that induce hepatic oxidative enzymes result in increased valproic acid clearance this increased clearance rate requires a higher dose to maintain effective therapeutic levels. 

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