Pharmacokinetic profile of loprazolam in 12 young and 12 elderly healthy volunteers.
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.
Dorling
M C
MC
HPRU Medical Research Center, University of Surrey, Egerton Road, Guildford, Surrey GU2 5XP, United Kingdom.
Hindmarch
I
I
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D014151:Anti-Anxiety Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001569:Benzodiazepines; D001682:Biological Availability; D004244:Dizziness / Q000139:chemically induced; D005221:Fatigue / Q000139:chemically induced; D006207:Half-Life; D006261:Headache / Q000139:chemically induced; D006801:Humans; D008875:Middle Aged; D007319:Sleep Initiation and Maintenance Disorders / Q000139:chemically induced; D012894:Sleep Stages / Q000187:drug effects
D014151:Anti-Anxiety Agents; D001569:Benzodiazepines; C020168:triazulenone