Valproate/valproic acid pharmacokinetics

Booth CL, Pollack GM, Brouwer KL. Hepatobiliary disposition of valproic acid and valproate glucuronide use of a pharmacokinetic model to examine the rate-limiting steps and potential sites of drug interactions. Hepatology 1996 23(4) 771-780. 

I Pharmacokinetics. Valproate sodium is rapidly converted to valproic acid in the stomach, whereas divalproex sodium delayed-release and extended-release tablets must pass into the small intestine to be converted to valproic acid. Valproic acid is highly bound to albumin and other plasma proteins, and it is extensively metabolized in the liver. A summary of the absorption, distribution, metabolism, and elimination data for valproate is found in Table 68-11. ... 

Two children taking valproic acid rapidly developed severe dyskinesias and bruxism after the first and second dose of methylphenidate, respectively. Valproate appears to potentiate the effects of methylphenidate, possibly by a pharmacokinetic mechanism, or because of additive dopaminergic effects. The authors of the re-... 

Amitriptyline and nortriptyline plasma levels can be increased by sodium valproate and valpromide, but in contrast, an isolated report attributes a paradoxical rise in serum desipramine levels to the withdrawal of valproic acid. Valproate pharmacokinetics may be moderately affected by amitriptyline. Status epilepticus has been attributed to elevated clomipramine levels in a patient taking valproic acid. 

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