Longitudinal study on pharmacodynamics and pharmacokinetics of acute, steady-state and withdrawn quazepam.

To assess pharmacodynamic and pharmacokinetic properties of acute, subchronic and withdrawn quazepam, a single-blind, longitudinal study was run in eight male, healthy young volunteers.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)