Clinical and Psychometric Effects of Flunitrazepam Observed during the day in Relation to Pharmacokinetic Data

Pharmacokinetics of Flunitrazepam after Single Rectal Administration in Children

“…This confirms the finding already published [9] about the existence of a strong correlation between the clinical effect and the central compartment concentration, contrary to a relatively weak correlation with the deep peripheral compartment concentration. Then, after single-dose administra tions, determination of flunitrazepam terminal elimination half-life value would be inadequate to define its duration of action.…”

Inter‐ and intraindividual variability in the concentration‐effect (sedation) relationship of flunitrazepam.

“…In a study by Amrein et al (1979) an EC50 of about 6 ng ml-1 was reported although no formal .inI concentration-response analysis was presented. Our study confirms the results of Amrein and co-workers (1979) However, this has been shown to produce somnolence during daytime, as also found in the present study.…”

“…The dose used for insomnia is 1 to 2 mg at night (Mattila & Larni, 1980). The pharmacokinetics of flunitrazepam have been studied extensively (Mattila & Larni, 1980) but the relationship between the sedative effect and plasma drug concentrations has not been characterized systematically, although there are reports indicating that the effect of flunitrazepam is closely related to the plasma concentration of unchanged drug (Amrein et al, 1979;McGowan et al, 1980). The purpose of this study 'was to investigate the relationship between the pharmacokinetics of flunitrazepam and its sedative effects in healthy volunteers after single oral dose given on two occasions.…”

Postural instability as a measure of sedative drug response.

“…Correlation of indices of benzodiazepine response with plasma concentrations may depend on the specificity of the method (Bittencourt et al, 1981) and perhaps on the timing of the observations, closer relationships being found at or about the distributive and post-distributive phases of the plasma concentration time profile than during the elimination phase (Amrein et al, 1979).…”