Computational strategies unravel and trace how liver disease changes hepatic drug disposition

Park, Sunwoo, Ropella, Glen E. P., Kim, Sean H. J., Roberts, Michael S. and Hunt, C. Anthony (2009) Computational strategies unravel and trace how liver disease changes hepatic drug disposition. Journal of Pharmacology and Experimental Therapeutics, 328 1: 294-305. doi:10.1124/jpet.108.142497


Author Park, Sunwoo
Ropella, Glen E. P.
Kim, Sean H. J.
Roberts, Michael S.
Hunt, C. Anthony
Title Computational strategies unravel and trace how liver disease changes hepatic drug disposition
Journal name Journal of Pharmacology and Experimental Therapeutics   Check publisher's open access policy
ISSN 0022-3565
1521-0103
Publication date 2009-01-01
Year available 2008
Sub-type Article (original research)
DOI 10.1124/jpet.108.142497
Volume 328
Issue 1
Start page 294
End page 305
Total pages 12
Place of publication Bethesda, MD, United States
Publisher American Society for Pharmacology and Experimental Therapeutics
Language eng
Abstract Liver disease changes the disposition properties of drugs, complicating drug therapy management. We present normal and “diseased” versions of an abstract, agent-oriented In Silico Livers (ISLs), and validate their mechanisms against disposition data from perfused normal and diseased rat livers. Dynamic tracing features enabled spatiotemporal tracing of differences in dispositional events for diltiazem and sucrose across five levels, including interactions with representations of lobular microarchitectural features, cells, and intracellular factors that sequester and metabolize. Differences in attributes map to measures of histopathology. We measured disease-causing differences in local, intralobular ISL effects, obtaining until now unavailable views of how and where hepatic drug disposition may differ in normal and diseased rat livers from diltiazem's perspective. Exploration of disposition in less and more advanced stages of disease is feasible. The approach and technology represent an important step toward unraveling the complex changes from normal to disease states and their influences on drug disposition.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ
Additional Notes Published online before print October 23, 2008

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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Created: Thu, 03 Sep 2009, 19:09:59 EST by Mr Andrew Martlew on behalf of School of Medicine