Disposition and metabolic fate of 14C-quazepam in man.
The absorption, metabolism, and excretion of quazepam, a new benzodiazepine hypnotic, was investigated in six normal male volunteers after oral administration of 25 mg 14C-quazepam in solution. Quazepam was well absorbed. Plasma radioactivity peaked (324.6 ng quazepam eq/ml) 1.75 hr postdose. Unchanged quazepam reached its maximum plasma level (148 ng/ml) at 1.5 hr with an apparent absorption half-life of 0.4 hr. Major plasma metabolites of quazepam were 2-oxoquazepam (OQ), obtained by replacement of S by O,N-desalkyl-2-oxoquazepam (DOQ), and 3-hydroxy-2-oxoquazepam (HOQ) glucuronide. Both OQ and DOQ are pharmacologically active. Plasma elimination half-lives for quazepam, OQ, DOQ, and radioactivity were 39, 40, 69, and 76 hr, respectively. The respective AUC (120 hr) values were 715, 438, 3323, and 11402 hr X ng/ml. Approximately 54% of the radioactive dose was excreted in the urine (31.3%) and feces (22.7%) over a 5-day period. HOQ glucuronide was the major urinary metabolite of quazepam. Other metabolites present in the urine in relatively large amounts were glucuronides of DOQ and HDOQ.
Zampaglione
N
N
Hilbert
J M
JM
Ning
J
J
Chung
M
M
Gural
R
R
Symchowicz
S
S
D000328:Adult; D014151:Anti-Anxiety Agents / Q000378:metabolism*; D001569:Benzodiazepines / Q000378:metabolism* / Q000652:urine; D001570:Benzodiazepinones / Q000378:metabolism; D001711:Biotransformation; D002849:Chromatography, Gas; D002855:Chromatography, Thin Layer; D005479:Flurazepam / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008297:Male
D014151:Anti-Anxiety Agents; D001570:Benzodiazepinones; D001569:Benzodiazepines; C039103:2-oxoquazepam; D005479:Flurazepam; C025130:quazepam; C020965:norflutoprazepam