ABSTRACT
A sensitive and specific gas chromatographic method, using an electron capture detector, for the measurement of plasma concentrations of loprazolam (HR-158) is described. Retention times of the hydrolysis product of loprazolam (2-amino-2'-chloro-5-nitrobenzophenone) and of the internal standard (2-amino-2'-fluorobenzophenone) were, respectively, 9 and 7 minutes. The sensitivity of the assay was 1.0 ng ml-1 of plasma, and for drug concentrations ranging from 1.0 to 15 ng ml-1 the mean recovery from plasma was 94.4 per cent and the mean coefficient of variation 9.8 per cent. This method was used to determine some pharmacokinetic parameters of loprazolam after administration of 2 X 1 mg capsule doses to nine healthy, fasted volunteers. The mean t 1/2 was 6.4 h, mean AUC infinity 65.42 ng.h ml-1, and the mean clearance 0.51 l min-1.
Subject(s)
Anti-Anxiety Agents/blood , Benzodiazepines , Benzodiazepinones/blood , Adult , Chromatography, Gas/methods , Humans , Kinetics , Male , Metabolic Clearance RateABSTRACT
Loprazolam is a benzodiazepine derivative which possesses, in animals, a potent hypnotic effect. In a double-blind single-dose study, three dose levels of loprazolam (0.5, 1.0, and 2.0 mg) were compared to each other as well as to 15 mg flurazepam and placebo in 60 insomniac outpatients. The 0.5- and 1.0-mg doses demonstrated hypnotic potency comparable to that of flurazepam, and all three treatments were superior to placebo. The hypnotic effect of the 2-mg dose of loprazolam was significantly greater than that of the other treatments, but at this dose, patients experienced significantly more side effects and morning hangover.
Subject(s)
Anti-Anxiety Agents/therapeutic use , Benzodiazepines , Benzodiazepinones/therapeutic use , Flurazepam/therapeutic use , Sleep Initiation and Maintenance Disorders/drug therapy , Adult , Aged , Anti-Anxiety Agents/adverse effects , Benzodiazepinones/adverse effects , Clinical Trials as Topic , Double-Blind Method , Female , Flurazepam/adverse effects , Humans , Male , Middle Aged , PlacebosABSTRACT
Large samples of adult American black and white males are being studied to determine the extent to which age and race are important factors in craniofacial mophology and growth. It is shown that a number of dentofaical dimensions continue to change throughout adulthood and that the amount and direction of these changes may be race-specific. Applications in orthodontics and prosthetic dentistry are indicated.
