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A systems biology approach to understanding elevated serum alanine transaminase levels in a clinical trial with ximelagatran.
- 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]
- Subjects :
- SERUM
ALANINE
CLINICAL trials
BIOMARKERS
CELL culture
Subjects
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