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Interactions between Verapamil and Digoxin in Langendorff-Perfused Rat Hearts: The Role of Inhibition of P-glycoprotein in the Heart.
MedLine Citation:
PMID:  20412466     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
P-glycoprotein (P-gp) is expressed in tumour cells as well as normal tissues including heart. Modulation of P-gp transport in vivo may lead to increased drug penetrance to tissues with resulting increases in toxicity. We aimed to investigate the effects of P-gp on the isolated heart by digoxin infusion in the absence and presence of verapamil. The study was performed in Langendorff isolated perfused rat hearts. After a 20 min. stabilisation period with Tyrode Buffer, digoxin (125 mug/5 mL) was infused for 10 min. in the control group (n = 7). The same dose of digoxin was infused during perfusion with verapamil (1 nm) containing Tyrode Buffer (n = 8) in the study group. Outflow concentration and cardiac parameters of digoxin were measured at frequent intervals for 40 min. AUEC((0-40 min)) for left ventricular developed pressure was significantly increased in the presence of verapamil (4260 +/- 39.37 mmHg min versus 4607 +/- 98.09 mmHg min; 95% CI -587.7 to -105.8; p = 0.0083). The significant increases in left ventricular developed pressure were at 20, 25, 30, 35 and 40 min. AUC((0-40 min)) value for outflow digoxin concentration-time curve was significantly lower in the presence of verapamil. Verapamil increased the positive inotropic effect of digoxin, probably through the inhibition of P-gp, which effluxes digoxin out of cardiac cells.
Authors:
Mualla Aylin Arici; Emrah Kilinc; Omer Demir; Mehmet Ates; Alaattin Yesilyurt; Ayse Gelal
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2010-4-20
Journal Detail:
Title:  Basic & clinical pharmacology & toxicology     Volume:  -     ISSN:  1742-7843     ISO Abbreviation:  -     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-4-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101208422     Medline TA:  Basic Clin Pharmacol Toxicol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Dokuz Eylul University, School of Medicine, Department of Pharmacology, Izmir, Turkey.
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