Linked Life Data

8730924

Source:http://linkedlifedata.com/resource/pubmed/id/8730924

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1996-10-2
pubmed:abstractText
1. An hplc method with fluorescence derivatization was developed for the quantification of remikiren in plasma (limit of quantification 2 ng/ml). This was used to determine the pharmacokinetics in various species of primate, in which the compound is a potent inhibitor of renin, as well as in the rat and dog in which it is less active. 2. After intravenous administration the mean residence time was < or = 1.5 h in all species, and the plasma clearance approached the corresponding hepatic blood flows. 3. Studies in the bile-duct cannulated rat and dog demonstrated that the high clearance was due to a combination of rapid metabolism, plus biliary and renal excretion of intact drug. 4. Consistent with the high hepatic clearance, oral bioavailability was low ( < or = 6%) in each species. However, all of the species tested absorbed a small proportion of an oral dose extremely rapidly, to give peak concentrations generally within 5 min of administration. 5. 'Simultaneous' collection of blood samples from the hepatic portal vein and aorta of rat confirmed that shortly after oral dosing the intact drug did cross the liver; however, the later collections contained predominantly more polar metabolites. 6. The rapid absorption of intact remikiren is consistent with the transient blockade of plasma renin activity, previously observed in primates after oral administration. However, the high clearance appears inconsistent with the subsequent prolonged decrease in blood pressure, suggesting that the latter effect is mediated through a 'tissue' compartment.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0049-8254
pubmed:author
pubmed:issnType
Print
pubmed:volume
26
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
333-45
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Pharmacokinetics of remikiren, a potent orally active inhibitor of human renin, in rat, dog and primates.
pubmed:affiliation
Pharma Division Preclinical Research, F. Hoffmann-La Roche AG, Basel, Switzerland.
pubmed:publicationType
Journal Article, Comparative Study