Detail of "7722-15-8"

Reference

Pharmacokinetic and biopharmaceutic profile of chlordiazepoxide hydrochloride in healthy subjects: multiple-dose oral administration

Pharmacokinetic and biopharmaceutic profile of chlordiazepoxide hydrochloride in healthy subjects: multiple-dose oral administration. Boxenbaum, H. G.; Geitner, K. A.; Jack, M. L.; Dixon, W. R.; Kaplan, S. A. (Dep. Biochem. Drug Metab.Some commonly used reagents like 438-41-5 and 1088-11-5 are used in this experiment., Hoffmann-La Roche Inc., Nutley, N. J., USA). J. Pharmacokinet. Biopharm., 5(1), 25-39 (English) 1977. CODEN: JPBPBJ. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacodynamics) Eight healthy male volunteers received chlordiazepoxide-HCl (I-HCl) [438-41-5] orally at a dosage of 10 mg every 8 h over a period of 21 days. On day 22, the regimen was changed to 30 mg every 24 h for an addnl. 15 days. Plasma concns. of I and its metabolites desmethylchlordiazepoxide [7722-15-8], demoxepam [963-39-3], and desoxydemoxepam [1088-11-5] were measured during 14 of the 36 treatment days. I plasma concn.-time data were consistent with first order absorption and complete bioavailability. The harmonic mean absorption half-life was 12.3 min. Disposition of I was described by a two-compartment open model with a harmonic mean terminal exponential half-life of 10.1 h. Average steady-state plasma levels of I, desmethylchlordiazepoxide, and demoxepam were approximately 0.75, 0.54, and 0.36 .mu.g/mL, resp. .

Effect of ketoconazole on hepatic oxidative drug metabolism

Effect of ketoconazole on hepatic oxidative drug metabolism. Brown, Michael W.; Maldonado, Alma L.; Meredith, Christopher G.; Speeg, K. V., Jr. (Health Sci. Cent., Univ. Texas, San Antonio, TX 78284, USA). Clin. Pharmacol. Ther. (St. Louis), 37(3), 290-7 (English) 1985. CODEN: CLPTAT. ISSN: 0009-9236. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The effect of ketoconazole [65277-42-1] on theophylline [58-55-9] and chlordiazepoxide [58-25-3] kinetics was studied in volunteers. These studies were performed before and after varying doses of ketoconazole within currently accepted therapeutic ranges. Ketoconazole had no effect on theophylline clearance, whereas the drug impaired chlordiazepoxide clearance from plasma. After a single dose of ketoconazole, there was a 20% decrease in clearance and a 26% decrease in vol. of distribution without evidence of inhibition of drug metab. These changes apparently were not related to ketoconazole dose. After receptive dosing with ketoconazole, chlordiazepoxide clearance decreased by 38% and was assocd. with reduced concns. of its first oxidative metabolite, N-desmethylchlordiazepoxide [7722-15-8]. Thus, ketoconazole inhibits at least 1 subset of the hepatic mixed-function oxidase [9040-60-2] system, but is not as general an inhibitor of hepatic oxidative drug metab. as cimetidine appears to be. For some coadministered drugs, ketoconazole may also have an effect on other kinetic parameters such as vol. of distribution. Therefore, clin. important drug interactions may occur with the concurrent use of ketoconazole.