Hepatic and Biliary Clearance

Question 1

Total clearance value calculated based on the plasma concentration-time data is considered the…

Answer 1

plasma clearance (CL)

Question 2

Blood clearance (CLblood) can be calculated based on the CL and plasma-to-blood conc. ratio (C/Cblood)

Answer 2

CLblood=CL*(C/Cblood)

Question 3

How to calculate fraction unbound in blood (fu,b)

Answer 3

fu,b = fu * (C/Cblood)

Question 4

Unbound clearance is always ________ than the total clearance because ___________.

Answer 4

greater; only unbound drug can be eliminated

Question 5

Hepatic clearance (CLh) can be defined as…

Answer 5

The volume of plasma (or blood for CLb,h) being cleared of drug per unit time during passage through the liver.

Question 6

When used in the calculation of excretion ratio (ER), CLh MUST be converted to CLb,h first

Answer 6

CLb,h = CL x (1-fe) x (C/Cblood)

Question 7

What is the ER?

Answer 7

ER -(extraction ratio) - I the fraction of blood being cleared during each pass through the liver

Question 8

CL b,h

Answer 8

hepatic (blood) clearance

Question 9

What cannot affect F?

Answer 9

Renal excretion cannot affect F

Question 10

Ff

Answer 10

fraction of dose that enters the gut wall

Question 11

Fg

Answer 11

fracton of dose in the gut wall that escapes elimination in the intestine

Question 12

Fh

Answer 12

fraction of dose in the portal system that escapes elimination in the liver

Question 13

If a drug is mainly eliminated in the liver and has a high ER value, its oral bioavailability should be-…

Answer 13

low

Question 14

What is CLint

Answer 14

CLint is the intrinsic clearance which represents the ability of the liver to remove the drug from blood when there is no restriction on blood flow to the liver

Question 15

The maximum possible value of CLb,h of any given drug is ___________ whereas here is ________ for the VLint value.

Answer 15

liver blood flow rate; no limit

Question 16

The maximum possible value of hepatic clearance is the _______

Answer 16

hepatic blood flow rate

Question 17

The maximum possible value of intrinsic clearance is_________

Answer 17

infinity

Question 18

High ER

Answer 18

ER > 0.7

Question 19

Low ER

Answer 19

ER < 0.3

Question 20

intermediate ER

Answer 20

ER = 0.3-0.7

Question 21

A decrease in hepatic blood flow will decrease __________ of a high ER drug

Answer 21

hepatic clearance

Question 22

Decrease in metabolizing enzyme activity will decrease ___________ of a high ER drug.

Answer 22

intrinsic clearance

Question 23

Decrease in hepatic blood flow will decrease _________ of a low ER drug.

Answer 23

neither hepatic nor intrinsic clearance

Question 24

Decrease in metabolizing enzyme activity will decrease ________ of a low ER drug.

Answer 24

both hepatic and intrinsic clearance

Question 25

Change in plasma protein binding will affect the hepatic clearance of _________ drugs

Answer 25

Low ER

Question 26

Change in plasma protein binding will affect the intrinsic clearance of _________ drugs

Answer 26

both low and high ER

Question 27

If a drug is 100% eliminated in the liver and has ER value of 0.88, its CL approximates ______

Answer 27

Qh

Question 28

If a drug is 100% eliminated in the liver and has ER value of 0.28, its CL approximates _______

Answer 28

fu*CL’int

Question 29

T/F - Does Css has an impact on fu

Answer 29

F - no impact of fu on Css

Question 30

T/F - Cu,ss has direct relationship between Cu,ss and fu

Answer 30

True

Question 31

For a high ER drug that is mainly eliminated in the liver, its total clearance approximates ________

Answer 31

hepatic blood flow rate

Question 32

For a low ER drug that is mainly eliminated in the liver, its total clearance approximates _________

Answer 32

intrinsic clearance (or the product of fraction unbound in blood and unbound intrinsic clearance)

Question 33

If a drug is mainly eliminated in the liver and has a volume of distribution valued of ~100L and a ER value greater than 0.7, its total clearance approximates _____ and its elimination half-life approximates.

Answer 33

CL~Qh; t1/2 = 0/693 x VT x fu/fuT/Qh

Question 34

If a drug is mainly eliinated in the liver and has a vol of distribution value of ~100L and a ER value of ~0.25, its total clearance approximates __________ and its unbound conc. at steady state approximates ___________.

Answer 34

CL~fuxCL’int; Cu,ss = fuxRo/fuxCL’int = R0/CL’int

Question 35

Biliary clearance is a proportionality constant relating _______ to ________.

Answer 35

excretion rate of unchanged drug in the bile; the plasma drug concentration

Question 36

Drugs and metabolites that have MW of _________ and are ________ and prone to biliary secretion

Answer 36

> 500 Da; polar

Question 37

Biliary excretion of a drug can be affected changes in ___________

Answer 37

active transporter activity