期刊
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY
卷 8, 期 5, 页码 316-325出版社
WILEY
DOI: 10.1002/psp4.12400
关键词
-
资金
- National Center for Advancing Translational Sciences of the National Institutes of Health [NIH-U24TR001951, NIH-5UH3TR000504, NIH-UG3TR002158, NIH-P30ES007033]
Drug-induced kidney injury, a major cause of acute kidney injury, results in progressive kidney disease and is linked to increased mortality in hospitalized patients. Primary injury sites of drug-induced kidney injury are proximal tubules. Clinically, kidney injury molecule-1, an established tubule-specific biomarker, is monitored to assess the presence and progression of injury. The ability to accurately predict drug-related nephrotoxicity preclinically would reduce patient burden and drug attrition rates, yet state-of-the-art in vitro and animal models fail to do so. In this study, we demonstrate the use of kidney injury molecule-1 measurement in the kidney microphysiological system as a preclinical model for drug toxicity assessment. To show clinical relevance, we use quantitative systems pharmacology computational models for in vitro-in vivo translation of the experimental results and to identify favorable dosing regimens for one of the tested drugs.
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