In vivo plasma protein binding interaction between valproic acid and naproxen

Roberto Grimaldi, Sergio Lecchini, Francesca Crema, Emilio Perucca

Research output: Contribution to journalArticlepeer-review


The effect of naproxen on the kinetics of free and total plasma valproic acid (VPA) was investigated in 6 normal volunteers by using a recently developed simple ultrafiltration technique associated with an immuno-enzymatic assay (Free Level System I, Syva). Each subject received a single oral dose of sodium valproate on two occasions: a) on a control day and b) during concurrent treatment with naproxen (500 mg b.i.d. for 5 consecutive days). Naproxen caused a slight but significant decrease in total plasma VPA levels but left free VPA levels essentially unchanghed. The free VPA fraction increased with increasing total VPA concentrations: at equivalent values of total VPA, however, the free fraction was higher in the presence of naproxen. It is concluded that naproxen exerts a moderate displacing effect on protein bound VPA, thereby increasing the clearence of total drug but leaving essentially unchanged the clearance of free drug.

Original languageEnglish
Pages (from-to)359-363
Number of pages5
JournalEuropean Journal of Drug Metabolism and Pharmacokinetics
Issue number4
Publication statusPublished - Oct 1984


  • drug interaction
  • naproxen
  • protein binding
  • Valproic acid

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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