Effects of temazepam on saccadic eye movements: concentration-effect relationships in individual volunteers.
Saccadic eye movements were analyzed after single oral doses of 20 mg temazepam and placebo in a randomized, double-blind crossover study in eight healthy volunteers. For an optimal evaluation of concentration-effect relationships, 18 blood samples and 43 effect measures were obtained over 33 1/2 hours. After placebo, saccadic peak velocity decreased within the first hour, with average values remaining 6.2% to 12.1% below baseline up to 15 hours after intake. After temazepam, significant changes in peak velocity occurred for 5 hours, with maximum decreases averaging 29.2% (95% confidence interval, 10.0 to 37.2). The apparent duration of effects ranged from 3 to 9 hours in individual subjects. Linear concentration-effect relationships were demonstrated for peak velocity, with individual slopes ranging from -0.11 to -0.46 deg/sec.(ng/ml)-1 (average r = -0.82, all p < 0.01). Differences in protein binding of temazepam did not account for the approximate fourfold variability in individual sensitivities to temazepam. By increasing the frequency of measurements, the accuracy of pharmacodynamic evaluations was clearly enhanced in this study.
van Steveninck
A L
AL
Centre for Human Drug Research, Leiden University Hospital, The Netherlands.
Verver
S
S
Schoemaker
H C
HC
Pieters
M S
MS
Kroon
R
R
Breimer
D D
DD
Cohen
A F
AF
D000328:Adult; D000704:Analysis of Variance; D001794:Blood Pressure / Q000187:drug effects; D002940:Circadian Rhythm / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D012016:Reference Values; D012044:Regression Analysis; D012438:Saccades / Q000187:drug effects* / Q000502:physiology; D013693:Temazepam / Q000493:pharmacokinetics / Q000494:pharmacology*
D013693:Temazepam