Effects of intravenous temazepam. II. A study of the long-term reproducibility of pharmacokinetics, pharmacodynamics, and concentration-effect parameters.
OBJECTIVE
To evaluate the long-term reproducibility of pharmacokinetic, pharmacodynamic, and concentration-effect parameters after intravenous administration of temazepam.


METHODS
Nine healthy volunteers were studied. Temazepam, 0.4 mg/kg, was infused intravenously for 30 minutes on two occasions 6 months apart. Venous plasma concentrations of temazepam were measured by HPLC in samples obtained between 0 and 24 hours. Pharmacodynamic effects were evaluated up to 8 hours for saccadic peak velocity and electroencephalogram (EEG) beta amplitudes. Subjects' state and trait anxiety were assessed by use of the Spielberger anxiety inventory.


RESULTS
Significant correlations between occasions were found for area under the plasma concentration-time curve (AUC) values (r = 0.91; p < 0.01) but not for maximum concentration and half-life. Significant correlations were also found for area under the effect-time curve (AUEC) values of peak velocity (r = 0.88; p < 0.01) but not for peak velocity (r = 0.48; p > 0.05). Significant differences between the slopes of concentration effect plots on different occasions were observed in two subjects for EEG beta and in three subjects for peak velocity, with one subject showing a similar change for both parameters. Trait anxiety scores were higher on the first occasion (33 +/- 7) than on the second occasion (29 +/- 7; p < 0.01). A negative correlation was found between trait anxiety scores and the slopes of concentration-effect plots for peak velocity (r = -0.63; p < 0.01).


CONCLUSIONS
For AUC and AUEC values the results indicate a reasonable long-term reproducibility of differences between subjects in the pharmacokinetics and pharmacodynamics of temazepam. However, there were limitations to the predictive value of derived concentration-effect parameters.
van Steveninck
A L
AL
Center for Human Drug Research, Leiden University Hospital, The Netherlands.
Schoemaker
H C
HC
den Hartigh
J
J
Pieters
M S
MS
Breimer
D D
DD
Cohen
A F
AF
D000293:Adolescent; D000328:Adult; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D016014:Linear Models; D008297:Male; D012016:Reference Values; D015203:Reproducibility of Results; D012438:Saccades / Q000187:drug effects; D013693:Temazepam / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
D013693:Temazepam