Linked Life Data

9698289

Source:http://linkedlifedata.com/resource/pubmed/id/9698289

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
1998-8-31
pubmed:abstractText
Atorvastatin, [(R-(R,R)]-2-(4-fluorophenyl)-beta, delta-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenyl-amino)carbonyl] -1H-pyrrole-1-heptanoic acid calcium salt (CI-981, AT), is a second generation 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor approved for clinical use as a cholesterol lowering agent. The disposition and metabolism of AT, including potential CYP450 induction, was investigated in mice administered an oral dose of [14C]AT (free acid) on study days 1 and 14. Peak plasma radioactivity concentrations occurred 1 hr postdose after both single- and multiple-dose administration and declined rapidly thereafter. Total plasma radioactivity levels in mice receiving the multiple dose were approximately 50% of levels observed after single-dose administration. Plasma metabolic profiles, which provided evidence of extensive metabolism, remained similar. Feces was the major route of AT-derived radioactivity elimination. Fecal profiles showed extensive metabolism with qualitatively similar profiles after single- and multiple-dose administration; however, quantitative differences were apparent. Metabolites identified in plasma and feces include hydroxylated, beta-oxidized, and unsaturated derivatives of AT. Most metabolites had undergone beta-oxidation. In mice receiving multiple 1 mg/kg doses of AT, no effect on spectral P450 concentration was found, and only a minor increase was observed at the 200 mg/kg dose level. Catalytic activities of CYP4501A, -2B, and -3A were not significantly affected; CYP4A activity decreased in a dose-dependent manner. Administration of multiple doses resulted in lower systemic plasma levels of total AT-derived radioactivity not readily explained by these studies. In mice, the majority of metabolites are formed primarily through the beta-oxidation pathway.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0090-9556
pubmed:author
pubmed:issnType
Print
pubmed:volume
26
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
755-63
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Metabolism and excretion studies in mouse after single and multiple oral doses of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor atorvastatin.
pubmed:affiliation
Department of Pharmacokinetics and Drug Metabolism, Parke-Davis Pharmaceutical Research Company, Ann Arbor, MI 48106, USA.
pubmed:publicationType
Journal Article