The pharmacokinetics of loprazolam have been studied in eight healthy male volunteers after single and repeated 2 mg oral doses taken at night, for eight nights. The absorption and disposition of unchanged drug (HPLC-GC assay) and receptor active benzodiazepine-type materials (radioreceptor assay) were examined after the first and eighth dose. Maximum levels of approximately 10 ng ml-1 (range 3.6 to 15.5 ng ml-1) were reached within about 2.5 h after dosing. The post-peak levels declined in a single exponential fashion with an overall mean +/- SD half-life of 7.06 +/- 1.98 h and total areas under the curve ranging from 35.9 to 189.0 ng ml-1 h. There were no statistical differences between the values for the first and eighth doses. There was no evidence to suggest that significant accumulation of parent drug or receptor active benzodiazepine-type materials had occurred, and it is concluded that the kinetics of loprazolam would allow repeated daily doses of 2 mg.

benzodiazepines: Relationship between sleep parameters and pharmacokinetics of loprazolam. Drug Dev. Res. 3:143-152, 1983. In the search for a relationship between subjective and electrophysiologic sleep parameters and blood levels of loprazolam during night sleep after single and repeated administration, eight normal volunteers took loprazolam, a novel imidazo-benzodiazepine, on eight consecutive evenings. The assessment of the pharmacokinetics of the drug was done by two different methods: a high-pressure liquid chromatography-gas chromatography (HPLC-GC) measuring the parent drug specifically and a radioreceptor assay (RRA) measuring both the parent drug and the metabolites binding to the benzodiazepine-receptor; the latter gave slightly higher values indicating the existence of metabolites binding to the benzodiazepinereceptor. The elimination half-life of the parent drug was about eight hr and did not significantly increase after repeated administration; the half-life when using the RRA was somewhat longer since steady state was not reached until the fourth day. A relationship was looked for between pharmacokinetic data and either self-evaluated or polygraphic sleep parameters obtained from all-night recordings on the first and eighth treatment nights. No correspondence could be demonstrated, suggesting that the drug does not act directly on sleep systems and that its hypnotic effects may be indirect, secondary to anxiolytic effects or to deactivation of wake systems.