Linked Life Data

17315538

Source:http://linkedlifedata.com/resource/pubmed/id/17315538

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2007-2-23
pubmed:abstractText
The In vitro metabolism of two alpha-1A-adrenergic antagonists, RWJ-69205 and RWJ-69471 (phthalimide-phenylpiperazine analogs), was assessed after 30 and 60 min incubations with rat, dog and human hepatic S9 fractions in the presence of an NADPH-generating system. Unchanged RWJ-69205 (> or = 72% of the sample in all species) plus 3 metabolites from the RWJ-69205 incubations, and unchanged RWJ-69471 (> or = 60% of the sample in all species) and 7 metabolites from the RWJ-69471 incubations, were profiled, quantified, and tentatively identified on the basis of API-MS and MS/MS data. The formation of RWJ-69205 and RWJ-69471 metabolites are via the following five metabolic pathways: 1. phenylhydroxylation, 2. O-dealkylation, 3. oxidative N-dealkylation, 4. N-dephenylation, and 5. dehydration. Pathway 1 formed 2 major/moderate hydroxy-phenyl metabolites of 2 analogs (4-17%) in all species, and pathway 2 produced 2 O-desisopropyl metabolites of 2 analogs in major/moderate (7-16%) in rat and human, and in trace (< 1%) in dog; in conjunction with pathway 1, yielded a minor diphenolic metabolite (< 1-2%) in RWJ-69471. Pathway 3 formed a minor N-dealkylated metabolite, isopropoxyphenyl piperazine (< 1-6%) in all species of 2 analogs. Pathways 4 and 5 produced 2 minor N-desphenyl metabolite and dehydrated metabolite, respectively, in rat and human S9 (< or = 1-2%) in RWJ-69471. Both RWJ-69205 and RWJ-69471 were less extensively metabolized in the dog. However, rat and human appeared to metabolize RWJ-69471 more extensively than RWJ-69205 in this hepatic system.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0378-7966
pubmed:author
pubmed:issnType
Print
pubmed:volume
31
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
271-6
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:17315538-Adrenergic alpha-1 Receptor Antagonists, pubmed-meshheading:17315538-Adrenergic alpha-Antagonists, pubmed-meshheading:17315538-Animals, pubmed-meshheading:17315538-Biotransformation, pubmed-meshheading:17315538-Chromatography, High Pressure Liquid, pubmed-meshheading:17315538-Dealkylation, pubmed-meshheading:17315538-Dogs, pubmed-meshheading:17315538-Humans, pubmed-meshheading:17315538-Hydroxylation, pubmed-meshheading:17315538-Isoindoles, pubmed-meshheading:17315538-Liver, pubmed-meshheading:17315538-Molecular Structure, pubmed-meshheading:17315538-Oxidation-Reduction, pubmed-meshheading:17315538-Phthalimides, pubmed-meshheading:17315538-Piperazines, pubmed-meshheading:17315538-Rats, pubmed-meshheading:17315538-Receptors, Adrenergic, alpha-1, pubmed-meshheading:17315538-Spectrometry, Mass, Electrospray Ionization, pubmed-meshheading:17315538-Tandem Mass Spectrometry, pubmed-meshheading:17315538-Time Factors
pubmed:articleTitle
Hepatic metabolism of two alpha-1A-adrenergic receptor antagonists, phthalimide-phenylpiperazine analogs (RWJ-69205 and RWJ-69471), in the rat, dog and human.
pubmed:affiliation
Johnson & Johnson Pharmaceutical Research & Development, L.L.C., Spring House, PA 19477, USA.
pubmed:publicationType
Journal Article, In Vitro