| Autor: |
McBurney RN; BG Medicine, Inc., Waltham, MA 02451, USA. rmcburney@bg-medicine.com, Hines WM, Von Tungeln LS, Schnackenberg LK, Beger RD, Moland CL, Han T, Fuscoe JC, Chang CW, Chen JJ, Su Z, Fan XH, Tong W, Booth SA, Balasubramanian R, Courchesne PL, Campbell JM, Graber A, Guo Y, Juhasz PJ, Li TY, Lynch MD, Morel NM, Plasterer TN, Takach EJ, Zeng C, Beland FA |
| Jazyk: |
angličtina |
| Zdroj: |
Toxicologic pathology [Toxicol Pathol] 2009 Jan; Vol. 37 (1), pp. 52-64. Date of Electronic Publication: 2009 Jan 26. |
| DOI: |
10.1177/0192623308329287 |
| Abstrakt: |
Drug-induced liver injury (DILI) is the primary adverse event that results in withdrawal of drugs from the market and a frequent reason for the failure of drug candidates in development. The Liver Toxicity Biomarker Study (LTBS) is an innovative approach to investigate DILI because it compares molecular events produced in vivo by compound pairs that (a) are similar in structure and mechanism of action, (b) are associated with few or no signs of liver toxicity in preclinical studies, and (c) show marked differences in hepatotoxic potential. The LTBS is a collaborative preclinical research effort in molecular systems toxicology between the National Center for Toxicological Research and BG Medicine, Inc., and is supported by seven pharmaceutical companies and three technology providers. In phase I of the LTBS, entacapone and tolcapone were studied in rats to provide results and information that will form the foundation for the design and implementation of phase II. Molecular analysis of the rat liver and plasma samples combined with statistical analyses of the resulting datasets yielded marker analytes, illustrating the value of the broad-spectrum, molecular systems analysis approach to studying pharmacological or toxicological effects. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
