Document Detail


Arterial vasodilating profile and biological effects of pinacidil in healthy volunteers.
MedLine Citation:
PMID:  2015168     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
1. The effects of pinacidil (25 mg, sustained release formulation) a) on systemic (arterial pressure, cardiac output) and regional (brachial and carotid arteries' diameters and flows) haemodynamics (pulsed Doppler techniques), b) on sympathetic (plasma noradrenaline) and renin-angiotensin (plasma renin activity) systems, and c) on atrial natriuretic factor have been investigated and compared with those of a placebo during the 12 h period following oral administration in a randomized, double-blind and cross-over study performed in six healthy volunteers. Simultaneously, the plasma levels of pinacidil and of its active metabolite, pinacidil N-oxide, were determined. 2. As compared with placebo, pinacidil decreased systemic vascular resistance and arterial blood pressure but cardiac output was not modified. 3. Pinacidil significantly increased brachial and carotid arteries' diameters (by 7 and 8% respectively) and flows (by 60 and 17% respectively) and decreased forearm vascular resistance (by 43%). Thus, pinacidil dilates both large and small arteries, increases large vessels' compliance and redistributes blood flow towards the muscular vascular bed. These effects peaked at 4 h and their duration at the brachial level was 8 h. 4. Pinacidil administration resulted in a stimulation of both sympathetic (increases in heart rate and plasma noradrenaline) and renin-angiotensin systems, and induced a transient increase in atrial natriuretic factor. 5. The duration of pinacidil haemodynamic effects at the brachial level is consistent with the pharmacokinetic data which show that pinacidil and pinacidil N-oxide plasma levels almost plateaued between 3 and 8, and 2 and 8 h respectively after oral administration of the sustained release formulation used.
Authors:
C Thuillez; E Pussard; E Bellissant; C Richer; R Kechrid; J F Giudicelli
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Publication Detail:
Type:  Clinical Trial; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of clinical pharmacology     Volume:  31     ISSN:  0306-5251     ISO Abbreviation:  Br J Clin Pharmacol     Publication Date:  1991 Jan 
Date Detail:
Created Date:  1991-05-23     Completed Date:  1991-05-23     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7503323     Medline TA:  Br J Clin Pharmacol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  33-9     Citation Subset:  IM    
Affiliation:
Service de Pharmacologie Clinique, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France.
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MeSH Terms
Descriptor/Qualifier:
Adult
Arteries / drug effects
Guanidines / adverse effects,  pharmacokinetics,  pharmacology*
Hemodynamics / drug effects
Hormones / blood
Humans
Pinacidil
Regional Blood Flow / drug effects
Renin-Angiotensin System / drug effects
Sympathetic Nervous System / drug effects
Vasodilation / drug effects*
Chemical
Reg. No./Substance:
0/Guanidines; 0/Hormones; 85371-64-8/Pinacidil
Comments/Corrections

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