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A systems biology approach to understanding elevated serum alanine transaminase levels in a clinical trial with ximelagatran.

Authors :
Andersson, Ulf
Lindberg, Johan
Wang, Shunghuang
Balasubramanian, Raji
Marcusson-Ståhl, Maritha
Hannula, Mira
Zeng, Chenhui
Juhasz, Peter J.
Kolmert, Johan
Bäckström, Jonas
Nord, Lars
Nilsson, Kerstin
Martin, Steve
Glinghammar, Björn
Cederbrant, Karin
Schuppe-Koistinen, Ina
Source :
Biomarkers; Dec2009, Vol. 14 Issue 8, p572-586, 15p, 1 Diagram, 3 Charts, 3 Graphs
Publication Year :
2009

Abstract

Ximelagatran was developed for the prevention and treatment of thromboembolic conditions. However, in long-term clinical trials with ximelagatran, the liver injury marker, alanine aminotransferase (ALT) increased in some patients. Analysis of plasma samples from 134 patients was carried out using proteomic and metabolomic platforms, with the aim of finding predictive biomarkers to explain the ALT elevation. Analytes that were changed after ximelagatran treatment included 3-hydroxybutyrate, pyruvic acid, CSF1R, Gc-globulin, L-glutamine, protein S and alanine, etc. Two of these analytes (pyruvic acid and CSF1R) were studied further in human cell cultures in vitro with ximelagatran. A systems biology approach applied in this study proved to be successful in generating new hypotheses for an unknown mechanism of toxicity. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
1354750X
Volume :
14
Issue :
8
Database :
Complementary Index
Journal :
Biomarkers
Publication Type :
Academic Journal
Accession number :
46748816
Full Text :
https://doi.org/10.3109/13547500903261354