Linked Life Data

1578380

Source:http://linkedlifedata.com/resource/pubmed/id/1578380

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1992-6-5
pubmed:abstractText
Conflicting information existed regarding the relevance of pharmacokinetics in relation to the duration of action of organic nitrates. We examined this question using three geometric isomers of organic mononitrates, L-isoidide mononitrate, isosorbide-2-mononitrate and isosorbide-5-mononitrate, which produce no active metabolites but possess diverse biological half-lives (T1/2). These compounds were given i.v. to rats at doses which were predetermined to produce equal peak effects on pulse pressure. The relationship between percentage change in pulse pressure and plasma mononitrate level could be described by the classical Hill equation, with similar slope but different EC50 values. A duration of action, defined as the time taken for the pulse pressure to change from -30% to -20% from base line, was measured experimentally. Theoretical analysis suggests that a linear relationship should exist between this duration of action and T1/2/slope, and this was indeed observed (r = 0.99, P less than .01, n = 12), affirming the dependency of pulse pressure pharmacodynamics on the pharmacokinetics of organic mononitrates. Pharmacokinetic modeling of the in vivo time-dependent hemodynamic effects further indicated that the blood compartment data were more consistent with a mechanism of mononitrate action that involves metabolic activation to form nitric oxide and cyclic GMP, rather than direct receptor activation. Using this pharmacodynamic model, the in vivo half-lives of nitric oxide and cGMP were estimated to be 1.6 and 2.0 min, respectively.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
261
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
692-700
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
Pharmacokinetic/pharmacodynamic relationship of the duration of vasodilating action of organic mononitrates in rats.
pubmed:affiliation
Department of Pharmaceutics, School of Pharmacy, State University of New York, Buffalo.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.