Document Detail


Influence of simvastatin at high dose and nifedipine on hemodynamic parameters in rabbits.
MedLine Citation:
PMID:  16531630     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Recent findings in vitro have shown that statins could reduce cardiomyocyte viability. The correlation between statin cardiotoxicity, assessed in vitro, and cardiac efficiency, investigated in vivo has not been estimated so far. The aim of the present experiment was to establish the impact of high-dose simvastatin on the hemodynamic parameters, especially on myocardium efficiency, after continuous infusion of dopamine. Moreover, hemodynamic interaction between simvastatin and nifedipine, metabolized by the same izoenzyme CYP3A4 was examined. The experiments were performed on twenty seven New Zealand white rabbits. The animals were divided into four groups receiving: 0.2% methylcellulose (MC) (control group), nifedipine, simvastatin or simvastatin + nifedipine, for 14 days (p.o.). The following hemodynamic parameters were estimated: cardiac output index (COI), heart rate (HR), systolic blood pressure (SBP), mean blood pressure (MBP), diastolic blood pressure (DBP) and total peripheral resistance index (TPRI). The registration of hemodynamic parameters was performed by Doppler method (Hugo Sachs Electronic Haemodyn). Dopamine did not cause a statistically significant increase in COI in rabbits receiving simvastatin alone or concomitantly with nifedipine. Nifedipine significantly lowered COI, BP and HR in rabbits if given simultaneously with simvastatin. In conclusion, administration of nifedipine may elicit detrimental impact on statin therapy, resulting in the worsening of cardiac performance. This may suggest another mechanism of drug-drug interaction than the one based on CYP3A4 inhibition.
Authors:
Magdalena Jasińska; Jacek Owczarek; Darla Orszulak-Michalak
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Pharmacological reports : PR     Volume:  58     ISSN:  1734-1140     ISO Abbreviation:  Pharmacol Rep     Publication Date:    2006 Jan-Feb
Date Detail:
Created Date:  2006-03-13     Completed Date:  2006-11-09     Revised Date:  2008-05-28    
Medline Journal Info:
Nlm Unique ID:  101234999     Medline TA:  Pharmacol Rep     Country:  Poland    
Other Details:
Languages:  eng     Pagination:  48-59     Citation Subset:  IM    
Affiliation:
Department of Biopharmacy, Medical University of Łódź, Muszyńskiego 1, PL 90-151 Łódź, Poland. magdajasinska@hotmail.com
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Pressure
Cardiac Output
Cytochrome P-450 Enzyme System / physiology
Dopamine / administration & dosage,  pharmacology*
Drug Antagonism
Heart Rate
Hemodynamics / drug effects*
Nifedipine / administration & dosage,  pharmacology*
Rabbits
Simvastatin / administration & dosage,  pharmacology*
Chemical
Reg. No./Substance:
21829-25-4/Nifedipine; 79902-63-9/Simvastatin; 9035-51-2/Cytochrome P-450 Enzyme System

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


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