| Clinical pharmacokinetics of levorotatory and racemic disopyramide, at steady state, following oral administration in patients with ventricular arrhythmias. | |
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MedLine Citation:
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PMID: 2482304 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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P Le Corre; D Gibassier; C Descaves; P Sado; J C Daubert; R Le Verge |
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Publication Detail:
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Type: Clinical Trial; Comparative Study; Journal Article; Randomized Controlled Trial |
Journal Detail:
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Title: Journal of clinical pharmacology Volume: 29 ISSN: 0091-2700 ISO Abbreviation: J Clin Pharmacol Publication Date: 1989 Dec |
Date Detail:
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Created Date: 1990-03-08 Completed Date: 1990-03-08 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0366372 Medline TA: J Clin Pharmacol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1089-96 Citation Subset: IM |
Affiliation:
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Laboratoire de Pharmacie Galénique et Biopharmacie, Université de Rennes, France. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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3737-09-5/Disopyramide |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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