Hepatic Drug Extraction Ratios: High vs. Low Clearance

hat does a HIGH extraction ratio indicate?

The liver removes a large percentage of the drug during one pass (ER ≥ 0.7).

What does a LOW extraction ratio indicate?

The liver removes a small percentage of the drug during one pass (ER ≤ 0.3).

Why categorize drugs as high- or low-extraction?

Because they respond differently to changes in blood flow, enzyme activity, and protein binding.

How is extraction ratio related to first-pass metabolism?

It determines how much drug the liver removes before the drug reaches systemic circulation.

Why do high-extraction drugs often have LOW oral bioavailability?

The liver removes a large percentage of the drug during first-pass metabolism, leaving less drug to reach systemic circulation.

What factor MOST influences clearance of HIGH-extraction drugs?

Hepatic blood flow. High-extraction drugs are FLOW-LIMITED.

Why can congestive heart failure alter clearance of high-extraction drugs?

It decreases cardiac output and hepatic blood flow, reducing drug clearance.

What happens to high-extraction drug clearance when hepatic blood flow decreases?

Clearance decreases because less drug is delivered to the liver.

Why does enzyme induction have limited effects on some high-extraction drugs?

Their clearance is primarily limited by blood flow rather than enzyme capacity.

Why do changes in protein binding have little effect on high-extraction drug clearance?

Their clearance is primarily controlled by hepatic blood flow.

What factors primarily determine clearance of LOW-extraction drugs?

Enzyme activity, intrinsic metabolic capacity, and the unbound fraction of the drug.

Why does enzyme inhibition decrease clearance of low-extraction drugs?

Low-extraction drugs depend on liver enzymes for metabolism. Inhibition decreases metabolism and clearance.

How does hypoalbuminemia affect a highly protein-bound, low-extraction drug?

Decreased albumin increases the free drug fraction, which can increase hepatic clearance.

Why are low-extraction drugs called CAPACITY-LIMITED?

Their clearance depends primarily on the liver's enzyme activity and ability to metabolize drugs, not blood flow.

How can severe liver disease affect high- and low-extraction drugs differently?

Low-extraction drug clearance decreases mainly from reduced enzyme capacity; high-extraction drug clearance may decrease from reduced hepatic blood flow and liver function.

Which drug is more affected by CYP450 inhibition: high- or low-extraction?

LOW-extraction drugs because their clearance depends more heavily on CYP450 enzyme activity.