JPET Introducing ALZET?ew Model 2006 Pump

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wyss, P. A.
Right arrow Articles by Bickel, M. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wyss, P. A.
Right arrow Articles by Bickel, M. H.

Single-dose kinetics of tissue distribution, excretion and metabolism of amiodarone in rats

PA Wyss, MJ Moor and MH Bickel

Department of Pharmacology, University of Berne, Switzerland.

In order to better understand the pharmacokinetic differences between acute and chronic regimens of the basic lipophilic antiarrhythmic, amiodarone (AM), a mass-balanced single-dose study ([14C]AM, 50 mg/kg, i.v.) was carried out until total elimination had been achieved (10 days). Total drug, AM and desethylamiodarone (DEA) were determined in plasma, eight tissues and excreta of rats with constant body weight. Three exponential terms were sufficient to describe the plasma concentration-time curve of unchanged AM with a long terminal half-life of 131 hr. An equally long terminal half-life of AM could also be observed in all tissues investigated. After 5 min, 42% of the radioactivity appeared in the liver, where it underwent redistribution to muscle, skin and, ultimately, adipose tissues. Whereas plasma and liver contained mainly unidentified metabolites and little DEA, unchanged AM predominated in all other tissues. According to the time- integrated parameters of distribution, AM has a potential to accumulate in adipose tissue under chronic administration. In contrast, DEA accumulation would be likely to occur in lean tissues, mainly in the lung. In 10 days, 94% of the injected radioactivity was excreted in feces and less than 2% in urine. Almost all of the excreted radioactivity consisted of unidentified metabolites, indicating that both AM and DEA are eliminated by metabolism.

Volume 254, Issue 2, pp. 502-507, 08/01/1990
Copyright © 1990 by American Society for Pharmacology and Experimental Therapeutics




This article has been cited by other articles:


Home page
 Drug Metab. Dispos.Home page
C. A. Evans, L. J. Jolivette, R. Nagilla, and K. W. Ward
EXTRAPOLATION OF PRECLINICAL PHARMACOKINETICS AND MOLECULAR FEATURE ANALYSIS OF "DISCOVERY-LIKE" MOLECULES TO PREDICT HUMAN PHARMACOKINETICS
Drug Metab. Dispos., July 1, 2006; 34(7): 1255 - 1265.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
A. Shayeganpour, A. O. S. El-Kadi, and D. R. Brocks
DETERMINATION OF THE ENZYME(S) INVOLVED IN THE METABOLISM OF AMIODARONE IN LIVER AND INTESTINE OF RAT: THE CONTRIBUTION OF CYTOCHROME P450 3A ISOFORMS
Drug Metab. Dispos., January 1, 2006; 34(1): 43 - 50.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
X.-J. Du, M. D. Esler, and A. M. Dart
Sympatholytic Action of Intravenous Amiodarone in the Rat Heart
Circulation, January 15, 1995; 91(2): 462 - 470.
[Abstract] [Full Text]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1990 by the American Society for Pharmacology and Experimental Therapeutics.