NDLI: Prediction of Clinically Relevant Safety Signals of Nephrotoxicity through Plasma Metabolite Profiling

Content Provider	PubMed Central
Author	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. Ruiz-noppinger, P. Piccoli, S. P.
Copyright Year	2013
Abstract	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.
Related Links	http://dx.doi.org/10.1155/2013/202497
Starting Page	202497
File Format	PDF
ISSN	23146133
e-ISSN	23146141
Journal	BioMed Research International
Volume Number	2013
Language	English
Publisher	Hindawi Publishing Corporation
Publisher Date	2013-01-01
Access Restriction	Open
Rights Holder	Hindawi Publishing Corporation
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Immunology and Microbiology Medicine Biochemistry, Genetics and Molecular Biology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Molecular Identification and Susceptibility of Clinically Relevant Scedosporium spp. in China

A new and clinically relevant murine model of solid-organ transplant aspergillosis

Searching for Clinically Relevant Biomarkers in Geriatric Oncology

Prophylaxis of Contrast-Induced Nephrotoxicity

Effect of Algae and Plant Lectins on Planktonic Growth and Biofilm Formation in Clinically Relevant Bacteria and Yeasts

Evaluation of clinically relevant changes in patient reported outcomes in knee and hip osteoarthritis: the minimal clinically important improvement

Gamma Knife Surgery as Monotherapy with Clinically Relevant Doses Prolongs Survival in a Human GBM Xenograft Model

Assessment of the clinically relevant change in pain for patients with sciatica

Src transduces erythropoietin-induced differentiation signals through phosphatidylinositol 3-kinase

Prediction of Clinically Relevant Safety Signals of Nephrotoxicity through Plasma Metabolite Profiling

Similar Documents

Molecular Identification and Susceptibility of Clinically Relevant Scedosporium spp. in China

A new and clinically relevant murine model of solid-organ transplant aspergillosis

Searching for Clinically Relevant Biomarkers in Geriatric Oncology

Prophylaxis of Contrast-Induced Nephrotoxicity

Effect of Algae and Plant Lectins on Planktonic Growth and Biofilm Formation in Clinically Relevant Bacteria and Yeasts

Evaluation of clinically relevant changes in patient reported outcomes in knee and hip osteoarthritis: the minimal clinically important improvement

Gamma Knife Surgery as Monotherapy with Clinically Relevant Doses Prolongs Survival in a Human GBM Xenograft Model

Assessment of the clinically relevant change in pain for patients with sciatica

Src transduces erythropoietin-induced differentiation signals through phosphatidylinositol 3-kinase

Prediction of Clinically Relevant Safety Signals of Nephrotoxicity through Plasma Metabolite Profiling