Valproic acid binding to human serum albumin and human plasma: Effects of ph variation and buffer composition in equilibrium dialysis

Fiorenzo Albani, Roberto Riva, Manuela Contin, Agostino Baruzzi

Research output: Contribution to journalArticlepeer-review

Abstract

The binding of valproic acid (VPA) to human serum albumin (HSA) and to pooled human plasma has been investigated by using equilibrium dialysis with three different dialysis solutions: phosphate buffer (solution I), Krebs solution (solution II), and Krebs solution without calcium (solution III). The effect of pH variation from 6.4 to 8.2 has been also investigated. VPA free fraction increased by increasing pH with all the dialysis solutions (from 4.1% at pH 6.4 to 9.4% at pH 8.2 with solution I, from 8.1% to 11.3% with solution II, and from 10.6% to 14.3% with solution III, in plasma). At each pH value, free fraction obtained with solution III was the highest and that obtained with solution I was the lowest. Data in plasma and HSA solution were similar. In a separate experiment we compared (at pH 7.4, with plasma) the three more frequently used dialysis solutions: phosphate buffer, phosphate buffer with NaCl, and Krebs solution. They gave, respectively, a mean VPA free fraction of 7.8, 10.3, and 12.7%. These findings can explain the wide range of VPA free fraction values reported in the literature. Researchers intending to determine VPA free concentration by equilibrium dialysis should take into account these methodological aspects.

Original languageEnglish
Pages (from-to)31-33
Number of pages3
JournalTherapeutic Drug Monitoring
Volume6
Issue number1
Publication statusPublished - 1984

Keywords

  • Buffer effect on binding
  • Equilibrium dialysis
  • PH effect on binding
  • Valproic acid binding

ASJC Scopus subject areas

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

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