Interaction between valproic acid and aspirin in epileptic children: Serum protein binding and metabolic effects

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Abstract
In 5 of 6 epileptic children who were taking 18-49 mg/kg per day valproic acid (VPA), the steady-state serum free fractions of VPA rose from 12 to 43% when antipyretic doses of aspirin were also taken. Mean total VPA half-life (t1/2) rose from 10.4 .+-. 2.7 to 12.9 .+-. 1.8 h and mean free VPA t1/2 rose from 6.7 .+-. to 2.1 to 8.9 .+-. 3.0 h when salicylate was present in the serum. The in vitro albumin binding association constant (ka) for VPA was decreased by salicylate, but the in vivo ka value was not affected. In 12-h (trough) concentrations of free and total VPA were higher in the presence of serum salicylate in 5 of 6 patients. Renal excretion of unchanged VPA decreased in 5 of 6 patients, but the VPA carboxyl conjugate metabolite-excretion patterns were not consistently affected. Salicylate apparently displaced VPA from serum albumin in vivo, but the increased VPA t1/2 and changes in VPA elimination patterns suggest that serum salicylate also altered VPA metabolism.