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Effects of pentoxifylline and its metabolites on platelet aggregation in whole blood from healthy humans.

Magnusson, Marie; Gunnarsson, Margoth LU ; Berntorp, Erik LU ; Björkman, Sven and Höglund, Peter LU (2008) In European Journal of Pharmacology 581(3). p.290-295
Abstract
It is known that pentoxifylline inhibits platelet aggregation in vitro, but the effects from pentoxifylline and its main metabolites: 3,7-dimetyl-1(5 hydroxyhexyl)xanthine (R-M1 and S-M1), 3,7-dimetyl -1(4-carboxybutyl)xanthine (M4), 3,7-dimetyl -1(3-carboxypropyl)xanthine (M5), on platelet aggregation in whole blood in vitro and in vivo have not been studied. We found that pentoxifylline, rac-M1, R-M1, S-M1 and M4 significantly inhibit ADP induced platelet aggregation in whole blood in vitro in a concentration-dependent manner, R-M1 being the most potent followed by rac-M1, S-M1, pentoxifylline, and M4. In this series of experiments the effects on aggregation induced ATP-release were less pronounced and were only significant after... (More)
It is known that pentoxifylline inhibits platelet aggregation in vitro, but the effects from pentoxifylline and its main metabolites: 3,7-dimetyl-1(5 hydroxyhexyl)xanthine (R-M1 and S-M1), 3,7-dimetyl -1(4-carboxybutyl)xanthine (M4), 3,7-dimetyl -1(3-carboxypropyl)xanthine (M5), on platelet aggregation in whole blood in vitro and in vivo have not been studied. We found that pentoxifylline, rac-M1, R-M1, S-M1 and M4 significantly inhibit ADP induced platelet aggregation in whole blood in vitro in a concentration-dependent manner, R-M1 being the most potent followed by rac-M1, S-M1, pentoxifylline, and M4. In this series of experiments the effects on aggregation induced ATP-release were less pronounced and were only significant after treatment with pentoxifylline, rac-M1 and R-M1, but the potency order appears to be the same. Since the metabolites are not available for use in humans, and also since each substance would be extensively metabolised in vivo, we made an attempt to estimate the relative contribution of each substance to the total effect of pentoxifylline in vivo. Previously published concentrations of pentoxifylline and these metabolites in humans, after administration of pentoxifylline, were used in combination with the potency ratios from this study. The findings from these calculations were that the main effect in vivo comes from S-M1 followed by pentoxifylline, the other metabolites contribute less than 10% each. In conclusion: in the following potency order R-M1, rac-M1, pentoxifylline, S-M1 and M4 all have significant effects on platelet aggregation in whole blood in vitro. However, it appears that the main effects in vivo are caused by S-M1 and pentoxifylline. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
European Journal of Pharmacology
volume
581
issue
3
pages
290 - 295
publisher
Elsevier
external identifiers
  • pmid:18155691
  • wos:000253752600008
  • scopus:38949213020
ISSN
1879-0712
DOI
10.1016/j.ejphar.2007.11.054
language
English
LU publication?
yes
id
9f069b83-089e-499f-ad62-81348067e7f9 (old id 1034972)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18155691?dopt=Abstract
date added to LUP
2009-07-08 17:11:38
date last changed
2017-10-01 03:50:20
@article{9f069b83-089e-499f-ad62-81348067e7f9,
  abstract     = {It is known that pentoxifylline inhibits platelet aggregation in vitro, but the effects from pentoxifylline and its main metabolites: 3,7-dimetyl-1(5 hydroxyhexyl)xanthine (R-M1 and S-M1), 3,7-dimetyl -1(4-carboxybutyl)xanthine (M4), 3,7-dimetyl -1(3-carboxypropyl)xanthine (M5), on platelet aggregation in whole blood in vitro and in vivo have not been studied. We found that pentoxifylline, rac-M1, R-M1, S-M1 and M4 significantly inhibit ADP induced platelet aggregation in whole blood in vitro in a concentration-dependent manner, R-M1 being the most potent followed by rac-M1, S-M1, pentoxifylline, and M4. In this series of experiments the effects on aggregation induced ATP-release were less pronounced and were only significant after treatment with pentoxifylline, rac-M1 and R-M1, but the potency order appears to be the same. Since the metabolites are not available for use in humans, and also since each substance would be extensively metabolised in vivo, we made an attempt to estimate the relative contribution of each substance to the total effect of pentoxifylline in vivo. Previously published concentrations of pentoxifylline and these metabolites in humans, after administration of pentoxifylline, were used in combination with the potency ratios from this study. The findings from these calculations were that the main effect in vivo comes from S-M1 followed by pentoxifylline, the other metabolites contribute less than 10% each. In conclusion: in the following potency order R-M1, rac-M1, pentoxifylline, S-M1 and M4 all have significant effects on platelet aggregation in whole blood in vitro. However, it appears that the main effects in vivo are caused by S-M1 and pentoxifylline.},
  author       = {Magnusson, Marie and Gunnarsson, Margoth and Berntorp, Erik and Björkman, Sven and Höglund, Peter},
  issn         = {1879-0712},
  language     = {eng},
  number       = {3},
  pages        = {290--295},
  publisher    = {Elsevier},
  series       = {European Journal of Pharmacology},
  title        = {Effects of pentoxifylline and its metabolites on platelet aggregation in whole blood from healthy humans.},
  url          = {http://dx.doi.org/10.1016/j.ejphar.2007.11.054},
  volume       = {581},
  year         = {2008},
}