hepatic extraction ratio

The hepatic extraction ratio answers a simple question: of all the drug entering the liver in the blood, what fraction does the liver remove in a single pass? An extraction ratio of 0.9 means the liver strips out 90% on one trip through; 0.1 means it removes only a tenth.

Formally it is the difference between the drug concentration entering and leaving the liver, divided by the entering concentration — a number between 0 and 1. Drugs are loosely grouped as high-extraction (above about 0.7), intermediate, or low-extraction (below about 0.3), and this category dictates how their hepatic clearance behaves.

The extraction ratio is the key to predicting drug behavior. High-extraction drugs have low oral bioavailability because of a heavy first-pass effect, and their clearance is limited by liver blood flow ('flow-limited'). Low-extraction drugs are 'capacity-limited' — their clearance depends on enzyme activity and protein binding, making them the ones most affected by enzyme induction, inhibition, and changes in protein binding.