Ian Graham Sheppard

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

In five of six epileptic children who were taking 18 to 49 mg/kg/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 (t½) rose from 10.4 ± 2.7 to 12.9 ± 1.8 hr and mean free VPA t½ rose from 6.7 ± to 2.1 to 8.9 ± 3.0 hr 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. The 12‐hr (trough) concentrations of both free and total VPA were higher in the presence of serum salicylate in five of six patients. Renal excretion of unchanged VPA decreased in five of six patients, but the VPA carboxyl conjugate metabolite–excretion patterns were not consistently affected. Salicylate appeared to displace VPA from serum albumin in vivo, but the increased VPA t½ and changes in VPA elimination patterns suggest that serum salicylate also altered VPA metabolism.