In vivo plasma protein binding interaction between valproic acid and naproxen

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 o...

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Bibliographic Details
Published inEuropean journal of drug metabolism and pharmacokinetics Vol. 9; no. 4; p. 359
Main Authors Grimaldi, R, Lecchini, S, Crema, F, Perucca, E
Format Journal Article
LanguageEnglish
Published France 01.10.1984
Subjects
Adult
Blood Proteins - metabolism
Female
Humans
Kinetics
Male
Naproxen - blood
Protein Binding
Valproic Acid - blood
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Summary: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 unchanged. 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 clearance of total drug but leaving essentially unchanged the clearance of free drug.
ISSN:0378-7966
DOI:10.1007/BF03189686