Document Detail


Clinical pharmacokinetics of levorotatory and racemic disopyramide, at steady state, following oral administration in patients with ventricular arrhythmias.
MedLine Citation:
PMID:  2482304     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Electrophysiological effects, antiarrhythmic activity and kinetics of levorotatory disopyramide (R(-) DP) and racemic disopyramide (equimolar mixture of R(-) DP and S(+) DP) were compared in patients with ventricular arrhythmias. This double blind cross-over randomized trial was achieved, at steady-state, following oral administration of 200 mg three times a day. In comparison with baseline values, electrophysiological data indicated that R(-) DP and racemic DP prolonged, significantly and similarly, PR interval (+11.7% and +10%, respectively, P less than .01), and QTc interval (+9.2% and +7%, respectively, P less than .001), while QRS interval was not significantly affected. The antiarrhythmic activity, assessed by percent reduction in ventricular extrasystoles frequency, showed a similar efficiency of levorotatory and racemic DP: 80% and 74%, respectively (P = .24). Ventricular tachycardias disappeared with both treatments in the three patients concerned. During the racemic period, the mean total plasma clearance, expressed as CL/F, of S(+) DP (114.6 ml/min), was significantly lower than that of R(-) DP (157 ml/min), (P less than .001). The mean total plasma clearance of R(-) DP, during the levorotatory period (163 ml/min), did not differ from the respective value determined during the racemic period (P = .32). During the racemic period, the stereoselective difference in total plasma clearances, which is not observed when DP enantiomers are administered separately, may result from an increase in unbound fraction of R(-) DP, due to the presence of S(+) DP, which is known to be a potent displacer of R(-) DP.
Authors:
P Le Corre; D Gibassier; C Descaves; P Sado; J C Daubert; R Le Verge
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Publication Detail:
Type:  Clinical Trial; Comparative Study; Journal Article; Randomized Controlled Trial    
Journal Detail:
Title:  Journal of clinical pharmacology     Volume:  29     ISSN:  0091-2700     ISO Abbreviation:  J Clin Pharmacol     Publication Date:  1989 Dec 
Date Detail:
Created Date:  1990-03-08     Completed Date:  1990-03-08     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0366372     Medline TA:  J Clin Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1089-96     Citation Subset:  IM    
Affiliation:
Laboratoire de Pharmacie Galénique et Biopharmacie, Université de Rennes, France.
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MeSH Terms
Descriptor/Qualifier:
Administration, Oral
Adult
Aged
Cardiac Complexes, Premature / drug therapy*,  metabolism
Disopyramide / administration & dosage,  adverse effects,  pharmacokinetics*
Double-Blind Method
Female
Heart Ventricles
Humans
Male
Middle Aged
Randomized Controlled Trials as Topic
Stereoisomerism
Tachycardia / drug therapy*,  metabolism
Chemical
Reg. No./Substance:
3737-09-5/Disopyramide

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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