Effect of liver pathophysiology on hepatic pharmacokinetics

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The liver is the main organ in the body for the metabolism and biliary excretion of natural and foreign solutes. Various liver diseases such as cirrhosis, alcoholic liver disease, diet and drug induced fatty livers can affect the uptake and metabolism of drugs and their suitability- dosing needs. Some liver diseases such as fatty livers are very common but how rapidly drugs are metabolised in these patients is not well described. The work is important as it may help us better design new drugs and better choose which drugs to give and, if so, in what doses. In addition, many liver diseases require a biopsy for a definite diagnosis of the likely function of the liver. Estimation of liver function is particularly important in estimating whether there will be sufficient reserve on resection of a cancer or deciding if a liver transplant is needed. The liver is also a very complex organ which can trap or breakdown solutes by a range of different systems. Also of importance is how those diseases affect drug disposition in the liver given that an altered hepatic drug disposition may affect systemic response to the drugs and their metabolites. This work seeks to answer these questions.