Influence of plasma proteins on the onset of hypnotic action of intravenous midazolam

The action of midazolam is influenced by serum protein binding as seen in the relationship between the time of onset of action of a fixed dose of the drug and the plasma albumin. Pretreatment with intravenous aspirin produces a decrease in the in vitro binding of midazolam. In vivo this is manifest as an increase in the rapidity of action of the benzodiazepines. Probenecid pretreatment will also cause a decrease in the onset time of midazolam. However, this is not due to altered plasma protein binding of the sedative.