Abstract:
: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.
journal_name
Am Heart Jjournal_title
American heart journalauthors
Meinertz T,Brandstätter A,Trenk D,Jähnchen E,Ostrowski J,Gärtner Wdoi
10.1016/0002-8703(85)90671-4subject
Has Abstractpub_date
1985-03-01 00:00:00pages
644-8issue
3 Pt 2eissn
0002-8703issn
1097-6744pii
0002-8703(85)90671-4journal_volume
109pub_type
杂志文章abstract:BACKGROUND:Cardiac magnetic resonance (cMR) perfusion imaging is a promising technique to assess coronary artery disease (CAD). Our objective was to evaluate accuracy of various cMR imaging parameters to detect significant CAD as compared with angiography or fractional flow reserve (FFR). METHODS:We prospectively enro...
journal_title:American heart journal
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更新日期:2007-08-01 00:00:00
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journal_title:American heart journal
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更新日期:1977-04-01 00:00:00
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doi:10.1016/0002-8703(75)90191-x
更新日期:1975-06-01 00:00:00
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更新日期:1994-06-01 00:00:00
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更新日期:1991-07-01 00:00:00
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更新日期:2008-03-01 00:00:00
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journal_title:American heart journal
pub_type: 杂志文章
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更新日期:1989-07-01 00:00:00
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更新日期:1991-11-01 00:00:00
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更新日期:2008-05-01 00:00:00
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更新日期:2000-09-01 00:00:00
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更新日期:1991-02-01 00:00:00
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pub_type: 杂志文章
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更新日期:1995-05-01 00:00:00
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doi:10.1016/0002-8703(80)90617-1
更新日期:1980-06-01 00:00:00
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更新日期:2009-02-01 00:00:00
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pub_type: 杂志文章,多中心研究
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更新日期:2016-04-01 00:00:00
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pub_type: 杂志文章
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更新日期:1980-12-01 00:00:00
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更新日期:1981-02-01 00:00:00
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pub_type: 临床试验,杂志文章
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更新日期:2006-06-01 00:00:00