The liver has a large metabolic reserve, and it is only when disease becomes decompensated that important changes in drug handling occur. Parenchymal liver disease e.g. chronic viral or alcoholic liver disease, has more impact on hepatic drug-metabolising enzyme activity than primarily cholestatic conditions, e.g. primary biliary cirrhosis, although clearance of drugs eliminated mainly by biliary excretion will be impaired in the latter.
Hepatocellular injury (toxic, infectious) leads to decreased activity of drug-metabolising enzymes, which is reflected in diminished plasma clearance of drugs that are metabolised. There is much variation between patients, and often overlap with healthy subjects.
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