triazulenone and Headache

The aim of the study was to investigate the pharmacokinetic profile of acute and steady state doses of loprazolam (1 mg) following nighttime administration in 12 young (18-30 years) and 12 elderly (60-80 years) nonfasting subjects. Loprazolam blood plasma concentration was determined by high-performance liquid chromatography with ultraviolet absorption detection. The drug was isolated from the plasma using a solid phase extraction procedure. On day 1 subjects were breathalyzer and given a brief medical examination. Baseline blood samples (10 ml) were taken via a venous cannula at -1.5 to -0.25 h prior to drug administration. Loprazolam was administered at 21.00 and further blood samples were taken at 0.5, 1, 1.5, 2.0, 2.5, 3, 4, 5, 6, 8, 10, 12, 18 and 23.5 h (baseline sample for day 2). On subsequent days (days 2, 3 and 4) blood samples were taken at -0.5 and 2 h. The schedule for day 1 was repeated for day 5 with the test period ending at 21.30 on day 6. Significant changes in the pharmacokinetics of the drug were evident in the elderly volunteers compared with the young volunteers following steady state, where tmax was significantly prolonged (CI 90% = 0.80 to 1.25; p < 0.00006) and a decline was observed in peak plasma concentration (CI 90% = 0.80 to 1.25; p < 0.00006). However, no statistically significant difference was found between the two groups in either the elimination half-life of the drug or the area under the curve. Loprazolam appears to be well tolerated by both the young and the elderly and only mild adverse effects were reported after nighttime administration. These results provide valuable data on the pharmacokinetics of the drug in normal clinical practice.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Anti-Anxiety Agents; Area Under Curve; Benzodiazepines; Biological Availability; Dizziness; Fatigue; Half-Life; Headache; Humans; Middle Aged; Sleep Initiation and Maintenance Disorders; Sleep Stages

One hundred and ninety-seven patients exhibiting a disturbed sleep pattern were recruited by thirty-five general practitioners into this single-blind randomized parallel group multicentre study. There were twelve patient withdrawals or drop-outs leaving sixty-one, sixty-three and sixty-one patients who, following 2 nights on placebo as baseline, completed 5 consecutive nights of treatment on loprazolam (1 mg), temazepam (20 mg) and placebo, respectively. Loprazolam and temazepam were found to have similar hypnotic activity with both treatments being superior to placebo. There was no statistical difference in the side-effect profile of the three treatment groups.

Topics: Adolescent; Adult; Anti-Anxiety Agents; Benzodiazepines; Benzodiazepinones; Clinical Trials as Topic; Female; Headache; Humans; Male; Placebos; Random Allocation; Sleep Initiation and Maintenance Disorders; Sleep Stages; Temazepam