Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/6018
Type: Journal article
Title: The enantiomer-specific kinetics and dynamics of verapamil after rapid intravenous administration to sheep: physiological analysis and modeling
Author: Huang, Y.
Upton, R.
Zheng, D.
Mclean, C.
Gray, E.
Grant, C.
Citation: Journal of Pharmacology and Experimental Therapeutics, 1998; 284(3):1048-1057
Publisher: American Society for Pharmacology and Experimental Therapeutics
Issue Date: 1998
ISSN: 1521-0103
1521-0103
Statement of
Responsibility: 
Yi Fei Huang, Richard N. Upton, Da Zheng, Colin Mclean, Elke C. Gray, and Cliff Grant
Abstract: The lung, myocardial and systemic kinetics of the enantiomers of verapamil, and their myocardial effects, were measured after administration of 10 mg of racemic verapamil during 2 min to chronically instrumented sheep; the data were used to develop a physiological model of the process. Verapamil was characterized by relatively slow transit through the lungs and heart. The lung kinetic values were membrane limited, whereas the tissue/blood equilibrium half-life for the heart was approximately 8 min. There was little difference between the kinetic values of the enantiomers, with the exception of their extent of deep distribution into the lung. The time course of the increase in myocardial blood flow caused by verapamil was best related to the time course of the arterial verapamil concentrations, whereas the time course of increases in the interval between P and R waves of the electrocardiogram and decreases in the maximum rate of rise of left ventricular pressure were best related to the time course of its myocardial concentrations. Thus, the observed hysteresis for these effects compared with arterial blood was largely caused by the time required for the myocardial equilibration. The model predicted that the myocardial concentrations of verapamil were relatively insensitive to the duration of injection of a given bolus dose, but that rapid injection caused transient, high arterial concentrations. It also predicted that the bolus dose of verapamil should be modified over a 2-fold range to account for physiologically plausible variations in base-line cardiac output and myocardial blood flow.
Keywords: Myocardium; Lung; Animals; Sheep; Verapamil; Calcium Channel Blockers; Stereoisomerism; Models, Biological
Rights: © 1998 by The American Society for Pharmacology and Experimental Therapeutics
RMID: 0030006068
Published version: http://jpet.aspetjournals.org/cgi/content/abstract/284/3/1048
Appears in Collections:Anaesthesia and Intensive Care publications

Files in This Item:
There are no files associated with this item.


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.