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In vivo plasma protein binding interaction between valproic acid and naproxen
European Journal of Drug Metabolism and Pharmacokinetics
|October 1, 1984
Summary
Naproxen slightly reduced total valproic acid (VPA) levels but did not change free VPA. This suggests naproxen moderately displaces protein-bound VPA, affecting total drug clearance.
Area of Science:
- Pharmacokinetics
- Drug Interactions
- Clinical Pharmacology
Background:
- Valproic acid (VPA) is an antiepileptic drug with a high protein binding rate.
- Understanding drug interactions is crucial for optimizing VPA therapy.
- Naproxen is a common nonsteroidal anti-inflammatory drug (NSAID).
Purpose of the Study:
- To investigate the effect of naproxen on the pharmacokinetics of free and total plasma valproic acid (VPA).
- To determine if naproxen alters VPA protein binding and subsequent drug clearance.
Main Methods:
- A study involving 6 healthy volunteers.
- Subjects received sodium valproate orally on two occasions: control and during naproxen treatment (500 mg twice daily for 5 days).
- Free and total plasma VPA levels were measured using ultrafiltration and an immuno-enzymatic assay.
Main Results:
- Naproxen administration resulted in a slight but significant decrease in total plasma VPA levels.
- Free VPA levels remained largely unchanged.
- The free VPA fraction increased with higher total VPA concentrations and was higher in the presence of naproxen.
Conclusions:
- Naproxen exerts a moderate displacing effect on protein-bound VPA.
- This displacement increases the clearance of total VPA but does not significantly alter the clearance of free VPA.
- Clinical implications suggest potential adjustments in VPA dosing when co-administered with naproxen.