Document Detail


Correlation of amiodarone dosage, heart rate, QT interval and corneal microdeposits with serum amiodarone and desethylamiodarone concentrations.
MedLine Citation:
PMID:  2816765     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Pharmacokinetic-dynamic relations for amiodarone have been difficult to define. Few studies have successfully correlated serum amiodarone concentration with either dose or pharmacodynamic effects. Reduction in heart rate, prolongation of corrected QT interval and accumulation of corneal microdeposits are 3 clinical effects well suited for making kinetic-dynamic comparisons because they occur in virtually all patients receiving amiodarone. Data on heart rate, corrected QT interval, corneal microdeposits, cumulative dose and serum concentrations of amiodarone and desethylamiodarone (DEA) were collected over the course of 1 year after initiation of therapy in 27 patients (mean age 55.4 +/- 2.35 years). Mean elimination half-lives in this study population were 56 days for amiodarone and 129 days for DEA, as estimated from cumulation kinetics without drug withdrawal. The extremely long half-lives of amiodarone and DEA make demonstration of steady-state concentration-response relations difficult. A new approach using analysis of sequential data before steady-state reveals general relations between dose, DEA concentration and 3 clinically observable effects of amiodarone. A linear relation was evident between DEA concentration and log mean cumulative amiodarone dose (mg/kg) for the population. The steep segments of the concentration-response curves for heart rate, microdeposits and corrected QT interval occurred at low, medium and high serum amiodarone and DEA concentrations, respectively. Patients not developing a decrease in heart rate or corneal microdeposits likely have very low serum drug concentrations and may not be adequately treated. The monitoring of heart rate, corrected QT interval and corneal microdeposits as an aid to assessing adequacy of amiodarone therapy requires further study.
Authors:
P T Pollak; A D Sharma; S G Carruthers
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The American journal of cardiology     Volume:  64     ISSN:  0002-9149     ISO Abbreviation:  Am. J. Cardiol.     Publication Date:  1989 Nov 
Date Detail:
Created Date:  1989-12-15     Completed Date:  1989-12-15     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0207277     Medline TA:  Am J Cardiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1138-43     Citation Subset:  AIM; IM    
Affiliation:
Department of Medicine, Victoria General Hospital, Dalhousie University, Halifax, Nova Scotia, Canada.
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MeSH Terms
Descriptor/Qualifier:
Amiodarone / administration & dosage*,  blood,  pharmacokinetics
Cornea / analysis*
Dose-Response Relationship, Drug
Electrocardiography*
Female
Follow-Up Studies
Half-Life
Heart Rate*
Humans
Male
Middle Aged
Prospective Studies
Time Factors
Chemical
Reg. No./Substance:
1951-25-3/Amiodarone; 83409-32-9/desethylamiodarone

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


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