Valproic acid free fraction in epileptic children under chronic monotherapy

Roberto Riva, Fiorenzo Albani, Emilio Franzoni, Emilio Perucca, Margherita Santucci, Agostino Baruzzi

Research output: Contribution to journalArticlepeer-review


The total and free (nonprotein-bound) concentration of valproic acid (VPA) was determined in plasma samples collected at two different times of the day (before the morning dose and 3 h later) in 62 epileptic children receiving maintenance single-drug therapy with sodium valproate. Both the total and the free concentrations were lower in the early than in the late morning samples (total VPA: 394.4 ± 150.0 vs. 556.9 ± 175.2 u.mol/L; free VPA: 20.1 ± 11.1 vs. 31.3 ± 17.4 μmol/L). The average free fraction of the drug was also lower in the early morning (4.8 ± 1.3 vs. 5.4 ± 1.6%, p <0.001). At both sampling times, the free fraction was positively correlated (p <0.01) with the total concentration. Evidence is presented that, at equal total plasma VPA concentration, the free fraction of the drug is significantly (p = 0.01) higher in the early than in the late morning samples. The rise in plasma free fatty acids (acting as displacing agents) after the overnight fast is probably responsible for this difference in free fraction. The implications of these findings with respect to the monitoring of free plasma VPA levels are discussed.

Original languageEnglish
Pages (from-to)197-200
Number of pages4
JournalTherapeutic Drug Monitoring
Issue number2
Publication statusPublished - 1983


  • Epileptic children
  • Plasma free concentrations
  • Plasma protein binding
  • Valproic acid

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology
  • Toxicology
  • Health, Toxicology and Mutagenesis
  • Biochemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Public Health, Environmental and Occupational Health


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