Document Detail

Kinetic analysis of myocardial uptake and negative inotropic effect of amiodarone in rat heart.
MedLine Citation:
PMID:  16574386     Owner:  NLM     Status:  MEDLINE    
The distribution kinetics of the highly lipophilic antiarrhythmic agent amiodarone is not well understood. The purpose of the present investigation was to develop a pharmacokinetic-pharmacodynamic (PK/PD) model to describe cardiac uptake and the negative inotropic effect of amiodarone in the isolated perfused rat heart. Amiodarone (10 microM) was infused for 15 min to 6 hearts. The time course of outflow concentration and left ventricular developed pressure were measured and analyzed by the model. The uptake of amiodarone by the heart was flow limited and characterized by an extremely high partition coefficient with a predicted tissue washout half-live of 17 h. Only 36.8% of input amount to heart recovered within 45 min after start of the 15 min infusion. The negative inotropic effect was delayed with a time constant of 11 min and the maximal decrease in left ventricular developed pressure was described by a sigmoid E(max) model with an E(max) of 37.7% and an EC(50) of 0.53 microM. Our results suggest a rapid tissue uptake and a moderate negative inotropic effect of amiodarone after intravenous injection.
Pakawadee Sermsappasuk; Myoungki Baek; Michael Weiss
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Publication Detail:
Type:  In Vitro; Journal Article     Date:  2006-03-29
Journal Detail:
Title:  European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences     Volume:  28     ISSN:  0928-0987     ISO Abbreviation:  Eur J Pharm Sci     Publication Date:  2006 Jun 
Date Detail:
Created Date:  2006-05-29     Completed Date:  2007-08-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9317982     Medline TA:  Eur J Pharm Sci     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  243-8     Citation Subset:  IM    
Section of Pharmacokinetics, Department of Pharmacology, Martin Luther University Halle-Wittenberg, D-06097 Halle, Germany.
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MeSH Terms
Amiodarone / metabolism*,  pharmacology
Anti-Arrhythmia Agents / metabolism*,  pharmacology
Heart / drug effects
Models, Biological
Myocardial Contraction
Myocardium / metabolism*
Rats, Wistar
Ventricular Function, Left
Ventricular Pressure
Reg. No./Substance:
0/Anti-Arrhythmia Agents; 1951-25-3/Amiodarone

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

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