Linked Life Data

8212733

Source:http://linkedlifedata.com/resource/pubmed/id/8212733

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1993-10-28
pubmed:abstractText
1. The pharmacokinetics of E6123, a platelet activating factor receptor antagonist, were studied after i.v. and oral administration to rat, guinea-pig, dog and rhesus monkey. Plasma concentrations of E6123 were determined by h.p.l.c. with UV detection. 2. After i.v. dosing (1 mg/kg), the plasma concentration-time curves fitted a two-compartment model. The half-lives for the terminal phases (t1/2) in rat, dog, and guinea-pig showed very little inter-individual variation, but t1/2 in the monkey (n = 4) varied more than four-fold. The distribution parameters were very similar in rat, dog and monkey (Vc and Vss approx. 1.2 and 1.5 l/kg, respectively) but slightly higher values were found in the guinea-pig, which also showed the lowest plasma protein binding. 3. After oral dosing (1 mg/kg), the maximum plasma concentrations were obtained within 0.3-3.0 h in all species. The half-life for each individual animal was almost the same as that after i.v. dosing. The mean bioavailabilities of E6123 in rat, guinea-pig and dog were about 65, 95 and 81%, respectively, but the values for monkey were again highly variable (range 32-99%). 4. The high variability in the monkey was confirmed by i.v. administration to a further 10 animals. The mean half-lives for the terminal phase in extensive metabolizers (EMs) (n = 4) and poor metabolizers (PMs) (n = 10) were approx. 1 and 4 h, respectively. 5. The rank order for total body clearance of E6123 was: rat > monkey (EMs) > dog > guinea-pig > monkey (PMs).
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0049-8254
pubmed:author
pubmed:issnType
Print
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
589-98
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Pharmacokinetics of a new thienodiazepine platelet activating factor receptor antagonist (E6123) in laboratory animals. Is there a metabolic polymorphism in the rhesus monkey?
pubmed:affiliation
Tsukuba Research Laboratories, Eisai Co., Ltd., Ibaraki, Japan.
pubmed:publicationType
Journal Article, Comparative Study