Relationships between plasma levels and psychological effects of benzodiazepines

In the past, pharmacokinetics of benzodiazepines have been extensively described. However, knowledge about relationships between their plasma levels and pharmacodynamic effects are scanty. Therefore, we investigated under several experimental conditions the disposition and the psychological response of the short acting midazolam (single dose 0,075 mg/kg i.v. and 15 mg po) and of the moderate long acting oxazepam (30 mg/die for 5 days). Psychological and psychomotoric effects were evaluated by analogue scales (sedation index), d-2 letter cancellation test, reaction time, critical flicker fusion frequency and adjective mood list. In general, good correlations were found between those tests and plasma levels, especially for midazolam. Analogue scales and reaction-time proved to be most useful in our "effect-kinetic" approach.