Valproate is eliminated almost entirely (>96%) by hepatic metabolism, and renal disease has little effect on valproate metabolism.71 However, valproate is 85–95% protein bound, and renal disease significantly affects valproate protein binding.71,72 In renal disease the total valproate plasma concentration falls, principally because of decreased protein binding, but the free valproate level is unchanged. (See Effects of renal impairment on steady-state plasma concentration of drugs for further discussion of this phenomenon.) Allosteric changes in protein binding73 and endogenous toxic products displacing valproate from protein binding sites74 may also contribute to decreased protein binding.
Reviewed and revised February 2004 by Steven C. Schachter, MD, epilepsy.com Editorial Board.
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