Longitudinal study on pharmacodynamics and pharmacokinetics of acute, steady-state and withdrawn quazepam.
To assess pharmacodynamic and pharmacokinetic properties of acute, subchronic and withdrawn quazepam, a single-blind, longitudinal study was run in eight male, healthy young volunteers. The design covered a 1-week placebo run-in period, a period with daily oral night-time administration of 15 mg quazepam until a pharmacokinetic steady-state was reached (3 weeks) and a 2-week placebo withdrawal period. Oculodynamic Test (ODT) (EOG-registration with simultaneous choice reaction task, CRT) and Adaptive Pursuit Tracking Test (APTT) were used for assessment of intradiurnal and long-term profiles of attention, perception, cognition, objective sedation, psychomotor and muscular (force-related) parameters and cardiorespiratory measures under workload. Visual analogue scales (VAS) of sedation, excitation and state anxiety were applied additionally. Plasma levels of quazepam and its metabolites (oxoquazepam and desalkyl-oxoquazepam) were intermittently analyzed by GC, within 24 h after actual blood sampling in the morning of assessment days, to check the attainment of the intended criterion for termination of medication (steady-state, "on-line kinetic procedure"). Adverse effects were recorded by subjects' written free recall and a symptom-checklist. Although a pharmacokinetic steady-state could be reached in sequence for the parent drug quazepam and its metabolites within 3 weeks, there was no pharmacodynamic steady-state at the end of this period, but a continuous impairment in oculomotor variables. Performance in the choice reaction task and the APTT showed a similar tendency, which was masked to a certain extend by learning effects. There were no signs for rebound effects within the 2 weeks after withdrawal. Relevant carry-over phenomena declined after 3 days of withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)
Schaffler
K
K
Institute for Pharmacodynamic Research, Munich, Fed. Rep. of Germany.
Kauert
G
G
Wauschkuhn
C H
CH
Klausnitzer
W
W
D000328:Adult; D014151:Anti-Anxiety Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D001569:Benzodiazepines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D001570:Benzodiazepinones / Q000378:metabolism; D004585:Electrooculography; D005479:Flurazepam / Q000031:analogs & derivatives / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D011597:Psychomotor Performance / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects; D012119:Respiration / Q000187:drug effects; D013375:Substance Withdrawal Syndrome / Q000523:psychology
D014151:Anti-Anxiety Agents; D001570:Benzodiazepinones; D001569:Benzodiazepines; C039103:2-oxoquazepam; D005479:Flurazepam; C025130:quazepam; C020965:norflutoprazepam