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Pharmacokinetics and metabolism of zopiclone

Pharmacokinetics and metabolism of zopiclone. Gaillot, J.; Heusse, D.; Houghton, G. W.; Aurele, J. Marc; Dreyfus, J. F. (Inst. Biopharm., Rhone-Poulenc, Antony, Fr.). Int. Pharmacopsychiatry, Volume Date 1982, 17(Suppl. 2), 76-91 (English) 1983. CODEN: INPHB6. ISSN: 0020-8272. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The pharmacokinetics and metab.Chemical with cas number 90297-40-8 also plays role. of a new hypnotic, zopiclone (ZD)(I) [43200-80-2], were studied under the following conditions: rats and dogs were given oral doses of the mol., 14C-labeled either on the side chain or on the pyrrolopyrazine nucleus; rats, rabbits and dogs were given increasing oral doses of the unlabeled compd.; human subjects in various physiopathol. situations - young and elderly healthy volunteers, patients with liver or renal impairments, nursing mothers - were given single or repeated doses, oral or i.v. (range 3.5-15 mg). ZD was rapidly and efficiently absorbed. Its oral bioavailability was >75% in all species except rats, where a first-pass effect of about 65% was recorded. Plasma protein binding was about 45%. The radioactive material rapidly diffused from the vascular compartment, with a marked affinity for the brain. Plasma kinetics of ZD were generally well described by a 2-compartment open model; in man, terminal half-life was 4-5 h, total body clearance was large (300 mL/min), and renal clearance very low (10 mL/min). The relationship between doses and concns., doses and urinary excretion of unchanged compd. and major metabolites was linear in all species, except rabbits. The major metabolic routes involved decarboxylation affecting more than 50% of dose (rats and dogs), N-desmethylation and N-oxidn.; more than 30% of the administered dose was found as the N-desmethyl [59878-63-6] and N-oxide deriv. [43200-96-0] in the urine of humans. Due to intensive metab., only 7-10% of the dose was recovered in urine and feces as unchanged compd. in all species. In nursing mothers, milk and plasma kinetics of ZD were similar with a milk/plasma ratio around 0.80. In human volunteers, the plasma half-life of ZD increased with age, whereas patients with liver or renal impairments showed little or no modification of pharmacokinetic parameters. .

Pharmacokinetics and metabolism of zopiclone

Pharmacokinetics and metabolism of zopiclone. Gaillot, J.; Heusse, D.; Hougton, G. W.; Aurele, J. Marc; Dreyfus, J. F. (Inst. Biopharm. Rhone-Poulenc, Antony F-92160, Fr.). Pharmacology, 27(Suppl. 2), 76-91 (English) 1983. CODEN: PHMGBN. ISSN: 0031-7012. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Pharmacokinetics and metab. of zopiclone (ZD) [43200-80-2] were studied under the following conditions: (1) rats and dogs were given oral doses of the drug 14C-labeled either on the side chain or on the pyrrolopyrazine nucleus; (2) rats, rabbits, and dogs were given increasing oral doses of the unlabeled compd.; (3) human subjects in various physiopathol. situations (young and elderly healthy volunteers, patients with liver or renal impairments nursing mothers) were given single or repeated doses, oral or i.v. (3.5-15 mg). ZD was rapidly and efficiently absorbed; its oral bioavailability was >75% in all species except rats, where a 1st-pass effect of ~65% was seen. Plasma protein binding was ~45%. The radioactive material rapidly diffused from the vascular compartment, with a marked affinity for the brain. Plasma kinetics of ZD were generally well described by a 2-compartment open model; in man, terminal half-life was 4-5 h; total body clearance was high (300 mL/mn), renal clearance very low (10 mL/min). The relation between doses and concns. and between doses and urinary excretion of unchanged compd. and major metabolites was linear in all species, except rabbits. The major metabolic routes involved decarboxylation, affecting >50% of the dose (rats and dogs), and N-demethylation and N-oxidn.: >30% as the N-demethyl [59878-63-6] and N-oxide [43200-96-0] derivs. in urine (humans). Due to extensive metab., only 7-10% of the dose was recovered in urine and feces as the unchanged compd. (all species). In nursing mothers, milk and plasma kinetics of ZD were similar; the milk-to-plasma ratio was ~0.80. In human volunteers, plasma half-life of ZD increased with age; patients with liver or renal impairments showed little or no modification of the pharmacokinetic parameters.Except for chemicals metioned above, 43200-96-0 and 59878-63-6 are also used. .