Kinetic and pharmacological studies on estazolam in mice and man.
After i.v. and oral doses of estazolam (5 mg/kg) to mice, the drug was rapidly cleared with a beta half-life (t1/2 beta) of 0.7 h. The active metabolite, 1-oxo-estazolam, was present in traces in mouse plasma and brain. Its elimination t1/2 (beta), determined after i.v. injection of 1-oxo-estazolam (5 mg/kg) to mice, was similar to that of the parent drug in both plasma and brain. After a single oral dose of estazolam (4 mg) to four human volunteers the drug was rapidly absorbed and reached maximum plasma concentrations in one to three hours. Elimination t1/2 of estazolam in humans was 19 h. The metabolite was undetectable in human plasma after either single or multiple doses of estazolam. These results, together with the finding that 1-oxo-estazolam was less effective than estazolam, in terms of ED50 and brain concentrations necessary to antagonize leptazol convulsions and disrupt rota-rod performance in mice, indicate that the metabolite does not contribute significantly to the pharmacological effects of its parent drug.
Mancinelli
A
A
Guiso
G
G
Garattini
S
S
Urso
R
R
Caccia
S
S
D000284:Administration, Oral; D000328:Adult; D000818:Animals; D014151:Anti-Anxiety Agents / Q000378:metabolism*; D004949:Estazolam / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism*; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D051379:Mice; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors
D014151:Anti-Anxiety Agents; C046063:1-oxoestazolam; D004949:Estazolam; D010433:Pentylenetetrazole