Reference

The disposition and metabolism of a hypnotic benzodiazepine, quazepam, in the hamster and mouse

The disposition and metabolism of a hypnotic benzodiazepine, quazepam, in the hamster and mouse. Hilbert, James; Pramanik, Birendra; Symchowicz, Samson; Zampaglione, Nicola (Dep. Drug Metab. Pharmacokinet., Schering-Plough Corp., Bloomfield, NJ 07003, USA). Drug Metab. Dispos., 12(4), 452-9 (English) 1984. CODEN: DMDSAI. ISSN: 0090-9556. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The disposition of 14C-labeled quazepam (I) [36735-22-5] was studied in hamsters and mice after i.v. and oral dosing. In both species, I was rapidly absorbed, as indicated by the plasma Cmax being reached within 1 h of an oral dose (5 mg/kg). Also, radioactivity is essentially completely absorbed in both species, since the percentage of dose excreted in the urine was not dependent on the route of drug administration. Radioactivity was widely distributed in the tissues of both species; however, it was concd. (relative to plasma) only in the liver and kidneys. In hamsters, 66-77% of the radioactivity was excreted within 48 h, and 97% within 7 days of dosing (57% found in urine and 40% in feces after i.v. dosing; 54% in urine and 43% in feces after oral dosing). In mice, 86-88% of the radioactivity was excreted within 24 h and 98% within 4 days of dosing (43% in urine and 56% in feces after i.v. dosing; 37% in urine and 61% in feces after oral dosing). In both species, plasma levels of I accounted for a very small percentage of plasma radioactivity and the elimination half-life was short (2.4 h in hamster and 1.2 h in mice), indicating extensive 1st pass metab. for this drug. 3-Hydroxy-N-desalkyl-2-oxoquazepam [17617-60-6], 3-hydroxy-2-oxoquazepam [87075-15-8], N-desalkyl-2-oxoquazepam [2886-65-9], and 2-oxoquazepam [49606-44-2] were identified as in the main urinary and blood metabolites. Quant. but not qual. differences between the 2 species were obsd. in quazepam metab.

Gas chromatographic determination of quazepam and two major metabolites in human plasma

Gas chromatographic determination of quazepam and two major metabolites in human plasma. Hilbert, James M.; Ning, James M.; Murphy, Gregory; Jimenez, Angel; Zampaglione, Nicola (Schering Corp., Bloomfield, NJ 07003, USA). J. Pharm. Sci., 73(4), 516-19 (English) 1984. CODEN: JPMSAE. ISSN: 0022-3549. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Two rapid, sensitive, and specific gas chromatog. (GC) methods for the quant. detn. of quazepam (I) [36735-22-5] and its major active plasma metabolites, the 2-oxo compd. (II) [49606-44-2] and the dealkylated oxo compd. (III) [2886-65-9], are described. The first measures I and II and the second measures III. The compds. are extd. from plasma with toluene and quantitated by electron-capture detection using the internal std. method. The methods are capable of quantitating plasma levels of I and II as low as 0.75 ng/mL and plasma levels of III as low as 1.5 ng/mL. Correlation coeffs. of std. curves were >0.9995 for all compds. Precision of the methods was measured at 2 different concns. for each compd.; the CV values were 3-6% for all 3 compds. The recovery of all comps. was >80%, and the ratio of recovery of each compd. to that of its internal std. did not vary at different concns., indicating appropriate internal stds. were selected for methods. Quazepam metabolites, other benzodiazepines, and drugs which are potential comedications do not interfere with either method. The methods were shown to be suitable for investigating the bioavailability and pharmacokinetics of quazepam at therapeutic doses.