| Pharmacokinetics and dynamic effects of diltiazem in the isolated guinea-pig heart. | |
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MedLine Citation:
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PMID: 3375187 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Myocardial pharmacokinetics of diltiazem showed two-compartment characteristics in the isolated, spontaneously beating guinea-pig heart. Half-times of initial and terminal drug accumulation phases were about 2.1 and 14.4 min., respectively. At 1 microgram ml-1 (2.4 microM) in the perfusion liquid the average concentration of diltiazem in the myocardium at steady state was about 16 micrograms g-1 (38.6 microM) with 17% referable to the deepest, possibly intracellular compartment. Increasing diltiazem concentrations from 13 to 889 ng ml-1 (31-2144 nM) produced a progressive increase in coronary flowrate from 100 to 174%. The computed Em- and EC50-values were 73.2% and 187 nM, respectively. Oxygen consumption decreased to 27.6% showing Em = 106% and IC50 = 1536 nM. Amplitude and velocity of myocardial contraction decreased to about 6% and 2%; Em = 101% and 104%, IC50 = 266 and 186 nM, respectively. Heart beating frequency decreased to 63% exhibiting Em = 58% and IC50 = 2015 nM. The PQ- and QRS-intervals increased to 133% and 112%, respectively. The frequency-corrected QT-interval decreased to 81.6%. Our findings demonstrate a relatively rapid and moderate accumulation of diltiazem in the guinea-pig heart accompanied by a marked increase in coronary flow, progressive and pronounced negative inotropic and chronotropic effects and a less than proportional decrease in oxygen consumption. |
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Authors:
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H K Jensen; F Nielsen-Kudsk |
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Publication Detail:
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Type: In Vitro; Journal Article |
Journal Detail:
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Title: Pharmacology & toxicology Volume: 62 ISSN: 0901-9928 ISO Abbreviation: Pharmacol. Toxicol. Publication Date: 1988 Mar |
Date Detail:
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Created Date: 1988-06-30 Completed Date: 1988-06-30 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8702180 Medline TA: Pharmacol Toxicol Country: DENMARK |
Other Details:
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Languages: eng Pagination: 166-71 Citation Subset: IM |
Affiliation:
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Institute of Pharmacology, University of Aarhus, Denmark. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Coronary Circulation / drug effects Diltiazem / pharmacokinetics*, pharmacology Female Guinea Pigs Heart / drug effects* Heart Rate / drug effects Male Myocardial Contraction / drug effects Myocardium / metabolism Oxygen Consumption / drug effects |
| Chemical | |
Reg. No./Substance:
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42399-41-7/Diltiazem |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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