Linked Life Data

3838400

Source:http://linkedlifedata.com/resource/pubmed/id/3838400

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3 Pt 2
pubmed:dateCreated
1985-4-19
pubmed:abstractText
The pharmacokinetic properties and hemodynamic effect of molsidomine and its pharmacologically active metabolite SIN-1 were investigated in 13 healthy volunteers following single oral doses. Hemodynamic changes were measured by finger plethysmography (peripheral arterial resistance), impedance plethysmography (venous distensibility), heart rate, and blood pressure. Plasma concentrations of molsidomine, SIN-1, and SIN-1C were measured by means of high-pressure liquid chromatography. Oral administration of rapidly dissolving tablets of molsidomine (2 tablets of 4 mg), a sustained-release form of molsidomine (8 mg), and SIN-1 (4 mg) caused an increase of the a/b ratio of the finger plethysmogram and an increase of the venous distensibility. Heart rate and blood pressure remained unaffected. The time course of the peripheral arterial effect mimicked the time course of plasma concentrations of molsidomine and SIN-1. Similar to the results in animals, molsidomine was metabolized in humans to SIN-1 and subsequently degraded to the inactive metabolite SIN-1C. The kinetic profile of both metabolites could be followed in the plasma. The rate-limiting step in the metabolic sequence of molsidomine was found to be enzymatic hydrolysis and decarboxylation of molsidomine to SIN-1. Concentration-response curves of the a/b ratio of the finger plethysmogram showed that the plasma concentrations required to produce a definite effect are much higher for molsidomine than for SIN-1. This shows that the pharmacodynamically active form of molsidomine in humans is the metabolite SIN-1. The changes in the finger plethysmogram produced by SIN-1 suggest that in addition to the effect on the venous site, SIN-1 also dilates the peripheral arterial site.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0002-8703
pubmed:author
pubmed:issnType
Print
pubmed:volume
109
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
644-8
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1985
pubmed:articleTitle
Relationship between pharmacokinetics and pharmacodynamics of molsidomine and its metabolites in humans.
pubmed:publicationType
Journal Article