Effect of Hepatic Disease on Pharmacokinetics: Active Drug, Metabolite and Fraction of Metabolized Drug

For many drugs, monitoring the concentrations of both the active drug and its metabolite is crucial as both contribute to the therapeutic effect.

In a patient with hepatic impairment, changes in liver function can alter drug potency. If the drug is more potent than its metabolite, liver impairment increases drug activity due to higher drug concentrations.

Conversely, if the metabolite is more potent than the drug, activity decreases due to reduced metabolite formation.

Liver impairment also affects drug elimination, which can be divided into two components: the fraction excreted unchanged and the fraction metabolized. The metabolized fraction is typically estimated from 1 - f_e.

Total body clearance can be calculated under the assumption that metabolism occurs in the liver, and the unchanged drug is excreted in the urine.

Drugs with a higher fraction of metabolized drugs are more significantly impacted by liver function changes, as they rely more on metabolism for elimination.