Hepatic extraction ratio

Question 1

Clearance definition

Answer 1

Volume of plasma/blood cleared of drug per unit time

Question 2

Hepatic extraction ratio = 1

Answer 2

Liver could remove all drug from body in 1st pass metabolism

Question 3

Hepatic extraction ratio = 0

Answer 3

No drug is removed as blood passes through the liver

Question 4

What determines hepatic clearance

Answer 4

Hepatic blood flow, extraction efficiency

Question 5

What is intrinsic clearance

Answer 5

Ability of liver to remove drug in absence of restrictions, measure of how active liver drug metabolising enzymes are

Question 6

CLint in low extraction ration drug

Answer 6

Very small

Question 7

High extraction ration drug

Answer 7

Intrinsic clearance much higher than liver blood flow, enzyme so active liver removes most-all drug presented, even protein bound drug can be stripped off

Question 8

What does oral administration introduce

Answer 8

First pass metabolism and bioavailability

Question 9

Bioavailability equation

Answer 9

F = 1 - EH

Question 10

Bioavailability of a low extraction ratio drug

Answer 10

Nearly all dose gets through liver first pass, bioavailability essentially complete, even if doubling or halving or minor portion removed little change in F

Question 11

Determinant of 1st pass metabolism and oral bioavailability in high extraction ratio drugs

Answer 11

Enzyme activity

Question 12

Major determinant of systemic clearance of high extraction ratio drugs

Answer 12

Hepatic blood flow

Question 13

Factors that influence hepatic clearance in low extraction ratio drugs

Answer 13

fu and CLint

Question 14

What is steady state concentration

Answer 14

Unbound drug able to interact with receptors

Question 15

CL for low extraction ratio

Answer 15

CL = fu.CLint

Question 16

CL for high extraction ratio

Answer 16

CL = QH