Which effect does severe hepatic disease have on drug protein binding?

Severe hepatic disease significantly alters the pharmacokinetics of drugs, particularly affecting drug protein binding. In healthy individuals, a considerable proportion of drugs are bound to plasma proteins, primarily albumin and alpha-1 acid glycoprotein. When hepatic function is compromised, the production of these binding proteins can be severely reduced, leading to a decrease in the overall protein binding capacity in the plasma.

As a result, with fewer binding sites available, more of the drug remains unbound, which increases the fraction of free (active) drug in the circulation. This unbound drug is often more pharmacologically active and can lead to an increased effect or toxicity. Therefore, in the context of severe hepatic disease, the availability of free drug is increased due to reduced protein binding capacity.

This understanding is crucial in adjusting drug dosages and monitoring therapeutic outcomes for patients with liver disease, ensuring safety and efficacy in pharmacotherapy.