Drug Clearance

Question 1

Drug clearance is measured in what units?

Answer 1

volume/time (mL/min)

Question 2

What is the formula(s) for Cl?

Answer 2

Cl = elimination rate (mg/min) / plasma conc (mg/mL)

Cl = Vd x K

Cl = Q x ER

Question 3

In the formula Cl = Q x ER,

What does Q and ER stand for?

Answer 3

Q = blood flow
ER = extraction ratio

Question 4

What does Clr stand for?

Answer 4

renal clearance

Question 5

What are the formula(s) for Clr?

Answer 5

Clr = Qu x Cu / Cp

Clr = filtration rate + secretion rate - reabsorption rate / Cp

Question 6

What is the clearance ratio?

Answer 6

Cl drug / Cl inulin

Question 7

If clearance ratio < 1 = ?

Answer 7

partially reabsorbed

Question 8

If clearance ratio = 1 ??

Answer 8

filtered only

Question 9

If clearance ratio > 1 = ??

Answer 9

actively secreted

Question 10

What is happening if the graph is curved?

Answer 10

You know that both secretion and filtration are happening

Question 11

What kind of graph would tell you that only filtration is happening?

Answer 11

straight line

Question 12

What is the formula for free amount of drug (Cpfree)

Answer 12

Cpfree = (1-alpha) Cp

free amount = free fraction x total amount

Question 13

What does (1-alpha) mean?

Answer 13

free amount

Question 14

What does fe stand for?

Answer 14

fraction of drug excreted

Question 15

What does R stand for?

Answer 15

infusion rate

Question 16

What does Css mean?

Answer 16

steady state [drug]

Question 17

What are the formulas for clearance after IV infusion?

Answer 17

Cl = R/Css
Cl = k x Vd

Question 18

What is hepatic clearance affected by?

Answer 18

• blood flow
• intrinsic Cl
• protein binding

Question 19

What does Clh mean?

Answer 19

hepatic clearance

Question 20

What is the formula for hepatic clearance?

Answer 20

Clh = [Q(Ca-Cv)]/Ca = Q x ER

Question 21

What does Ca mean?

Answer 21

arterial concentration

Question 22

What does Cv mean?

Answer 22

venous concentration

Question 23

What does Clint stand for?

Answer 23

intrinsic clearance

Question 24

For some drugs that are ____ extracted, the extraction ratio is greater than 0.7

Answer 24

highly

Question 25

What does highly extracted mean?

Answer 25

That the liver removes the drug almost as fast as its delivered to it.

Question 26

Highly extracted drugs: | An increase in blood flow will _____ the organ (hepatic) clearance rate.

Answer 26

increase

Question 27

Highly extracted drugs: Are known as _____ ____ limited or ____ ____ sensitive (same answer for both blanks)

Answer 27

blood flow

Question 28

Highly extracted drugs: | For drugs that affect ____ ______ it also decreases organ blood flow and as such will decrease its own clearance rate

Answer 28

cardiac output

Question 29

Drugs that are ____ extracted by the organ have an extraction ratio (ER) of about 0.1 to 0.4

Answer 29

poorly

Question 30

Poorly extracted drugs: | Does blood flow affect clearance rate?

Answer 30

No - a change in organ blood flow doesn't really affect the clearance rate.

Question 31

Poorly extracted drugs: | Drugs that are poorly extracted are known as ______ limited

Answer 31

enzyme

Question 32

Poorly extracted drugs: | If you induce the enzymes that are responsible for metabolizing the drugs, how will hepatic clearance be affected?

Answer 32

it will go up significantly.

Question 33

Poorly extracted drugs: | If you induce the enzymes that are responsible for metabolizing the drugs, how will biliary clearance be affected?

Answer 33

clearance will also go up for drugs eliminated via the biliary excretion

Question 34

Poorly extracted drugs: | Why do poorly extracted drugs have variable half-lives and clearance rates?

Answer 34

- because patients have much different timers of hepatic enzymes - thus, much different extraction ratios occur for the same drug in different people which results in much different clearance rates

Question 35

What is Intrinsic Clearance (Clint) used to describe?

Answer 35

- the ability of the liver to remove the drug in the absence of any flow limitation - this reflects the inherent activity of the mixed-function oxidases

Question 36

What does it mean if Q > Clint?

Answer 36

blood flow is not the limiting factor

Question 37

What does it mean if Clint > Q ?

Answer 37

you have tons of enzymes, they are not the limiting factor

Question 38

Drug protein binding is not a factor in hepatic clearance for drugs that have ___ extraction ratios

Answer 38

high

Question 39

Drugs that have low extraction ratios may be affected by plasma ____ _____ depending on the fraction of drug bound to proteins

Answer 39

protein binding

Question 40

For drugs that have low extraction ratios and low binding to plasma proteins, _____ changes in protein binding would not produce any significant changes in hepatic clearance

Answer 40

small

Question 41

Drugs with low extraction ratios and low binding to plasma proteins are ???

Answer 41

capacity-limited, binding insensitive drugs

Question 42

Drugs with low extraction ratios are high binding to plasma proteins are ??

Answer 42

capacity-limited binding sensitive drugs *because a small displacement in the protein binding of these drugs will cause a very large increase in the free drug concentration