Benzodiazepine-induced sedation and cortisol suppression. A placebo-controlled comparison of oxazepam and nitrazepam in healthy male volunteers.
The sedative and cortisol suppressing properties of oxazepam (45 and 60 mg) and nitrazepam (10 and 15 mg) were examined in eight healthy male subjects. The most clear differences between oxazepam and nitrazepam were those seen with respect to the time course and until maximal effect (Tmax) of the different measurements. Nitrazepam showed maximal sedation after 1 h, maximal benzodiazepine level (RRA), and reaction time prolongation after 2 h, and maximal cortisol suppression after 3 h. Oxazepam showed maximal sedation after 2 h, maximal benzodiazepine levels, reaction time prolongation and cortisol suppression after 3 h. After administration of oxazepam (both doses) a transient return to baseline levels of cortisol was demonstrated. Whereas the degree of sedation correlated significantly within drug groups with the concurrent benzodiazepine levels, the Tmax of sedation was recorded 1 h earlier than the peak blood concentration (RRA) for both nitrazepam and oxazepam. The time course for cortisol suppression for the two compounds differed clearly from the other measurements and was not related to the peak blood concentration.
Department of Clinical Pharmacology, Odense University, School of Medicine, Denmark.
P
P
Christensen
A
A
Lolk
L F
LF
Gram
P
P
Kragh-Sørensen
D000339:Affect / Q000187:drug effects; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D004311:Double-Blind Method; D006854:Hydrocortisone / Q000037:antagonists & inhibitors* / Q000097:blood; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D008297:Male; D009567:Nitrazepam / Q000494:pharmacology; D010076:Oxazepam / Q000494:pharmacology; D051381:Rats; D011930:Reaction Time / Q000187:drug effects
D014151:Anti-Anxiety Agents; D006993:Hypnotics and Sedatives; D010076:Oxazepam; D009567:Nitrazepam; D006854:Hydrocortisone