THE RELATIONSHIP BETWEEN CLINICAL EFFECT AND CONCENTRATIONS OF TEMAZEPAM IN PLASMA AND CEREBROSPINAL-FLUID

The clinical pharmacodynamics of temazepam were investigated in patien ts who received spinal anaesthesia. Total plasma and cerebrospinal flu id temazepam concentrations were measured and correlated with the clin ical effects. Sedation was measured by three separate methods. None, i ncluding an aggregated score of all three measures, was correlated clo sely with either the plasma or the cerebrospinal fluid levels (p = 0.8 6 and 0.12 respectively). Anxiety was measured before and after premed ication. The two scores were correlated but the change in anxiety afte r premedication did not correlate with either the plasma or the cerebr ospinal fluid concentrations (p = 0.11 and 0.45 respectively). Short-t erm memory was measured before and after premedication. The decline in short-term memory ability was moderately well correlated with both th e plasma and the cerebrospinal fluid levels (p = 0.0005 and 0.013 resp ectively). With temazepam, the variation in sedative and anxiolytic ef fects between subjects is explained not by differences in pharmacokine tics but rather by differences in the pharmacodynamic response. Becaus e sedative and anxiolytic effects are poorly correlated, but the amnes ic effect is well correlated with temazepam concentrations, different sites of action for these effects are suggested.