Prediction of Clinically Relevant Safety Signals of Nephrotoxicity through Plasma Metabolite Profiling
Joint Authors
Mattes, W. B.
Kamp, H. G.
Fabian, E.
Herold, M.
Krennrich, G.
Looser, R.
Mellert, W.
Prokoudine, A.
Strauss, V.
van Ravenzwaay, B.
Walk, T.
Naraoka, H.
Omura, K.
Schuppe-Koistinen, I.
Nadanaciva, S.
Bush, E. D.
Moeller, N.
Piccoli, S. P.
Ruiz-Noppinger, Patricia
Source
Issue
Vol. 2013, Issue 2013 (31 Dec. 2013), pp.1-12, 12 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2013-05-21
Country of Publication
Egypt
No. of Pages
12
Main Subjects
Abstract EN
Addressing safety concerns such as drug-induced kidney injury (DIKI) early in the drug pharmaceutical development process ensures both patient safety and efficient clinical development.
We describe a unique adjunct to standard safety assessment wherein the metabolite profile of treated animals is compared with the MetaMap Tox metabolomics database in order to predict the potential for a wide variety of adverse events, including DIKI.
To examine this approach, a study of five compounds (phenytoin, cyclosporin A, doxorubicin, captopril, and lisinopril) was initiated by the Technology Evaluation Consortium under the auspices of the Drug Safety Executive Council (DSEC).
The metabolite profiles for rats treated with these compounds matched established reference patterns in the MetaMap Tox metabolomics database indicative of each compound’s well-described clinical toxicities.
For example, the DIKI associated with cyclosporine A and doxorubicin was correctly predicted by metabolite profiling, while no evidence for DIKI was found for phenytoin, consistent with its clinical picture.
In some cases the clinical toxicity (hepatotoxicity), not generally seen in animal studies, was detected with MetaMap Tox.
Thus metabolite profiling coupled with the MetaMap Tox metabolomics database offers a unique and powerful approach for augmenting safety assessment and avoiding clinical adverse events such as DIKI.
American Psychological Association (APA)
Mattes, W. B.& Kamp, H. G.& Fabian, E.& Herold, M.& Krennrich, G.& Looser, R.…[et al.]. 2013. Prediction of Clinically Relevant Safety Signals of Nephrotoxicity through Plasma Metabolite Profiling. BioMed Research International،Vol. 2013, no. 2013, pp.1-12.
https://search.emarefa.net/detail/BIM-1030190
Modern Language Association (MLA)
Mattes, W. B.…[et al.]. Prediction of Clinically Relevant Safety Signals of Nephrotoxicity through Plasma Metabolite Profiling. BioMed Research International No. 2013 (2013), pp.1-12.
https://search.emarefa.net/detail/BIM-1030190
American Medical Association (AMA)
Mattes, W. B.& Kamp, H. G.& Fabian, E.& Herold, M.& Krennrich, G.& Looser, R.…[et al.]. Prediction of Clinically Relevant Safety Signals of Nephrotoxicity through Plasma Metabolite Profiling. BioMed Research International. 2013. Vol. 2013, no. 2013, pp.1-12.
https://search.emarefa.net/detail/BIM-1030190
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1030190