Document Detail


Evaluation of anti-platelet and anti-thrombotic effects of cilostazol with PFA-100® and Multiplate® whole blood aggregometer in vitro, ex vivo and FeCl3-induced thrombosis models in vivo.
MedLine Citation:
PMID:  21420150     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We evaluate the anti-platelet and anti-thrombotic effects of cilostazol using Multiplate® and PFA-100® in vitro and ex vivo with freshly isolated rat whole blood and in vivo venous and arterial thrombosis models in the same species, in an effort to assess the sensitivity of the whole blood aggregometer assays without potential issues of species differences. In vitro assay of anti-platelet effects of cilostazol against collagen-induced aggregation using Multiplate® produced a graded dose-dependent inhibition curve with IC50 value of 75.4 ± 2.4 μM while it showed a highly sensitive and all-or-none type inhibition response from 25 μM in PFA-100®. Interestingly, cilostazol manifested anti-thrombotic effects in vivo at much lower plasma concentrations than the effective concentrations measured in ex vivo or in vitro aggregation tests using PFA-100® or Multiplate®. In addition, the tail bleeding time measurement demonstrated that rats have lower sensitivity to the anti-platelet effects of cilostazol than mice. These results suggest that the detailed comparative evaluation of whole blood aggregometer assays with anti-thrombotic effects in vivo should be preceded before the application of these methods for the pharmacodynamic studies of anti-thrombotic agents.
Authors:
Chae-Wook Kim; Jun-Won Yun; Il-Hong Bae; Yang-Hui Park; Yeon Su Jeong; Jin Woo Park; Jin-Ho Chung; Young-Ho Park; Kyung-Min Lim
Publication Detail:
Type:  Journal Article     Date:  2011-03-21
Journal Detail:
Title:  Thrombosis research     Volume:  127     ISSN:  1879-2472     ISO Abbreviation:  Thromb. Res.     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-05-30     Completed Date:  2011-11-03     Revised Date:  2013-05-30    
Medline Journal Info:
Nlm Unique ID:  0326377     Medline TA:  Thromb Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  565-70     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Ltd. All rights reserved.
Affiliation:
Amorepacific CO R&D Center, Yongin 446-729, Republic of Korea.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Platelets / drug effects
Chlorides
Ferric Compounds
Fibrinolytic Agents / pharmacology*
Male
Mice
Mice, Inbred C57BL
Platelet Aggregation / drug effects
Platelet Aggregation Inhibitors / pharmacology*
Platelet Function Tests / methods
Rats
Rats, Sprague-Dawley
Tetrazoles / pharmacology*
Thrombosis / blood*,  chemically induced,  drug therapy*
Chemical
Reg. No./Substance:
0/Chlorides; 0/Ferric Compounds; 0/Fibrinolytic Agents; 0/Platelet Aggregation Inhibitors; 0/Tetrazoles; N7Z035406B/cilostazol; U38V3ZVV3V/ferric chloride

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


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