Document Detail

Bepridil, myocardial accumulation kinetics and dynamic effects in the isolated rabbit heart.
MedLine Citation:
PMID:  3263633     Owner:  NLM     Status:  MEDLINE    
Both myocardial uptake and disposition of bepridil in the isolated rabbit heart showed two-compartment characteristics which possibly reflects the existence of superficial and deep binding sites. Terminal accumulation and disposition half-lives were 218 and 196 min., respectively. The half-times of the initial distributory processes were about 33 min. At a drug concentration in the perfusion liquid of 0.54 micrograms ml-1 (1.27 microM) the average concentration of bepridil in the myocardium at steady state was about 489 micrograms g-1 (1161 microM) with 43% referable to the deepest, presumably intracellular compartment. Increasing bepridil concentrations from 3 to 2333 ng ml-1 (7-5542 nM) in the perfusion liquid caused a terminal decrease in coronary flowrate to 58% of the mean control flowrate. Amplitude and velocity of myocardial contraction both decreased in a biphasic way to about 28.6 and 13.6%, respectively. Apparent dynamic steady states developed within about 20 min. Inhibitory Em-values related to the first phase were 39.8 and 53.2%, and to the second phase 97.7 and 98.5%, respectively. Heart beating frequency also decreased biphasically to 53.9% and showed inhibitory Em-values of 17.2 and 47.5% related to the two phases. Myocardial oxygen consumption decreased to 55.6%. The electrocardiographic PQ- and QRS-intervals increased to 147 and 133%, respectively. The frequency-corrected QT-interval also increased significantly from 100 to 123%. Our findings demonstrate a slow and very pronounced accumulation of bepridil in the rabbit heart. Biphasic and very marked negative inotropic and chronotropic effects and a less than proportional decrease in oxygen consumption developed much faster.(ABSTRACT TRUNCATED AT 250 WORDS)
F Nielsen-Kudsk; J Askholt; P Jakobsen
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Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  Pharmacology & toxicology     Volume:  63     ISSN:  0901-9928     ISO Abbreviation:  Pharmacol. Toxicol.     Publication Date:  1988 Aug 
Date Detail:
Created Date:  1988-11-30     Completed Date:  1988-11-30     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8702180     Medline TA:  Pharmacol Toxicol     Country:  DENMARK    
Other Details:
Languages:  eng     Pagination:  122-8     Citation Subset:  IM    
Institute of Pharmacology, University of Aarhus, Denmark.
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MeSH Terms
Binding Sites
Calcium Channel Blockers / pharmacokinetics*,  pharmacology
Heart / drug effects*
Heart Rate / drug effects
Myocardium / metabolism*
Pyrrolidines / pharmacokinetics*,  pharmacology
Reg. No./Substance:
0/Calcium Channel Blockers; 0/Pyrrolidines; 64706-54-3/Bepridil

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

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