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Valproic acid and diazepam interaction in vivo.
British Journal of Clinical Pharmacology
|April 1, 1982
Summary
Valproic acid increases unbound diazepam levels by displacing it from protein binding sites. This drug interaction also affects diazepam
Area of Science:
- Pharmacokinetics
- Drug Metabolism
- Clinical Pharmacology
Background:
- Diazepam is commonly prescribed for anxiety and seizures.
- Valproic acid is an anticonvulsant and mood-stabilizing medication.
- Potential drug interactions between valproic acid and diazepam require investigation.
Purpose of the Study:
- To investigate the pharmacokinetic effects of sodium valproate on diazepam.
- To determine how valproate influences diazepam's distribution and elimination.
Main Methods:
- Six healthy volunteers received intravenous diazepam.
- Oral sodium valproate (1500 mg daily) was administered concurrently.
- Serum concentrations of unbound diazepam and its metabolite were measured.
Main Results:
- Valproate administration doubled the unbound fraction of diazepam.
- Apparent volume of distribution and plasma clearance of diazepam increased significantly.
- Serum N-desmethyldiazepam levels were significantly lower during coadministration.
Conclusions:
- Valproic acid displaces diazepam from plasma protein binding sites.
- Valproic acid inhibits the metabolism of diazepam.
- This interaction leads to higher unbound diazepam concentrations and altered elimination.