title: Effect of sodium valproate on midazolam distribution.
abstract: The displacement of midazolam, a new water-soluble, short acting benzodiazepine, from its plasma binding sites by sodium valproate, has been studied in man. An increase of its free fraction (ranging from 2.71 to 5.35%) in plasma from epileptic patients receiving sodium valproate was observed. A similar situation was created in rabbits by pretreatment with sodium valproate (600 mg kg-1 day-1) and posterior hypnosis with midazolam. Due to the interaction, sodium valproate-pretreated rabbits showed an increase in midazolam brain levels (130.91 micrograms g-1 in cortex vs 84.55 micrograms g-1 in control animals). Therefore, it seems likely that displacement of midazolam by sodium valproate in epileptic patients could lead to an increase of the midazolam response.
mesh_terms: D000328:Adult; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008874:Midazolam / Q000493:pharmacokinetics*; D008875:Middle Aged; D011485:Protein Binding / Q000187:drug effects; D011817:Rabbits; D014018:Tissue Distribution; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D001798:Blood Proteins; D014635:Valproic Acid; D008874:Midazolam