Document Detail


Myocardial pharmacokinetics of thiopental in sheep after short-term administration: relationship to thiopental-induced reductions in myocardial contractility.
MedLine Citation:
PMID:  8863278     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The myocardial kinetics and dynamics of thiopental (750 mg over 2 min) were examined in chronically instrumented sheep (five studies in four sheep). The myocardial kinetics were studied by simultaneous rapid sampling of arterial and coronary sinus blood for 30 min. The myocardial kinetics for four of the five studies were best described by a single flow-limited compartment with apparent volumes of between 42 and 113 mL. These volumes equated to half-lives of equilibration between blood and myocardium of between 0.49 and 1.00 min when baseline blood flow was taken into account. The remaining study was better described by a model with a slight membrane limitation (permeability/flow ratio of approximately 2). Myocardial contractility was studied as a measure of myocardial pharmacodynamics and was reduced to 53% of baseline at approximately 2.5 min after the start of the dose. Effect compartment analysis showed that there was hysteresis between the time course of these contractility changes and the time course of the arterial concentrations, with effect compartment half-lives between 0.08 and 0.87 min. There was significantly less hysteresis for the coronary sinus concentrations. It is concluded that thiopental equilibrated rapidly with a component of the myocardium, and that consequently its effects on myocardial contractillity also rapidly equilibrated with both afferent and effluent myocardial blood.
Authors:
R N Upton; Y F Huang; C Grant; E C Gray; G L Ludbrook
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of pharmaceutical sciences     Volume:  85     ISSN:  0022-3549     ISO Abbreviation:  J Pharm Sci     Publication Date:  1996 Aug 
Date Detail:
Created Date:  1997-01-30     Completed Date:  1997-01-30     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  2985195R     Medline TA:  J Pharm Sci     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  863-7     Citation Subset:  IM    
Affiliation:
Department of Anaesthesia and Intensive Care, Royal Adelaide Hospital, University of Adelaide, Australia.
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MeSH Terms
Descriptor/Qualifier:
Animals
Female
Heart / drug effects,  physiology
Hemodynamics / drug effects
Hypnotics and Sedatives / administration & dosage,  pharmacokinetics*,  pharmacology
Myocardial Contraction / drug effects*
Myocardium / metabolism*
Sheep
Thiopental / administration & dosage,  pharmacokinetics*,  pharmacology
Chemical
Reg. No./Substance:
0/Hypnotics and Sedatives; 76-75-5/Thiopental

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


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