Effects of liver diseases on drug metabolism.

Although the liver is the main site of drug metabolism, conflicting results have been reported on drug elimination during liver diseases. Drug metabolism may depend on histological changes in the liver (acute or chronic hepatitis, cirrhosis) but may also depend on their origin (viral, toxic or immunological). Drug metabolism is also influenced by the severity of liver dysfunction. Cytochrome P450 isozymes and conjugation pathways may be differently affected by these conditions, and specific probe drugs have to be used in order to study the effect of diseases on each enzyme of drug metabolism. Probe-based assays must be validated during disease, since the pharmacokinetics of the parent drug and/or of its metabolites may be altered. Because of these limitations, therapeutic drug monitoring may be the most reliable way to adjust drug dosing at present.