Differential effects of valproic acid on the serum protein binding of lorazepam and diazepam.

Valproic acid and free fatty acids have been shown to displace diazepam from its plasma binding sites both in vitro and in vivo. Since lorazepam exhibits a substantial degree of binding, but differs from other benzodiazepines in that no increase in its free fraction in serum is observed when free fatty acids are raised, the effect of valproate on the serum protein binding of diazepam and lorazepam was assessed. Sodium valproate produced a marked increase in the free fraction of diazepam, but practically no effect on the percentage of free lorazepam.