Linked Life Data

3772713

Source:http://linkedlifedata.com/resource/pubmed/id/3772713

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
1986-12-15
pubmed:abstractText
5-[(2-Aminoacetamido)methyl]-1-[p-chloro-2-(o-chlorobenzoyl)phenyl ]-N,N-dimethyl-1 H-s-triazole-3-carboxamide hydrochloride dihydrate (450191-S), a sleep inducer, is a ring-opened derivative of 1,4-benzodiazepine and has been reported to be activated by intestinal aminopeptidases. In order to determine the biopharmaceutical significance of 450191-S as the ring-opened derivative of 1,4-benzodiazepine, we examined plasma levels of active metabolites in rats following oral administration of 450191-S or its primary active metabolite, 8-chloro-6-(2-chlorophenyl)-N,N-dimethyl-4H-1,2,4-triazolo [1,5-a] [1,4]benzodiazepine-2-carboxamide (M-1). By increasing the dose of 450191-S, the plasma level of the active metabolites increased dose-dependently, which appeared to be due to saturation of hepatic elimination. The areas under the plasma concentration-time curves of active metabolites at a dose of 30 mg/kg of 450191-S were 2- to 20-fold higher than those at the same dose of M-1 administration per se. These results appeared to be attributable to the presence of a labile precursor of M-1, desglycylated 450191-S, which could avoid extensive first-pass extraction by the liver. In conclusion, the results suggested that 450191-S is superior to M-1, since the former maintained higher plasma levels of the active metabolites.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0386-846X
pubmed:author
pubmed:issnType
Print
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
563-9
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed:year
1986
pubmed:articleTitle
Biopharmaceutical characterization of 450191-S, a ring-opened derivative of 1,4-benzodiazepine. I. Active metabolite levels in rat plasma.
pubmed:publicationType
Journal Article