Agent-based simulation of drug disposition in cirrhotic liver

2010 
Cirrhosis, a chronic liver disease, alters hepatic drug disposition. Little is known about mechanisms underpinning the disease progression and how they contribute to changes in liver disposition properties. Here we present multilevel, agent-based and agent-directed In Silico Livers (ISLs) to probe plausible answers for a cationic drug, diltiazem, in two different types of cirrhotic rat livers. Starting with ISLs that validated against diltiazem disposition data from normal livers, we systematically transformed ISL characteristics to achieve validation against perfusion outflow profiles from the two types of diseased livers. For detailed analysis, we developed and implemented methods to trace each object representing diltiazem during simulated perfusion experiments. So doing enabled gaining heretofore-unavailable insight into plausible disposition details from diltiazem perspective in normal and diseased livers. From the results, we posit that changes in ISL micromechanistic details may have disease caused counterparts during disposition.
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