The Concept of Clearance

Question 1

What is clearance?

What is it commonly measured in?

Answer 1

The volume of body fluid cleared of a substance per unit time
litres/hour or ml/min

Question 2

Why is the parameter, clearance, useful?

Answer 2

• useful for judging the method of elimination or metabolism of a drug
• useful for quantitative predictions of changes in the plasma concentration of substances over time
• it can also be measured for specific organs. e.g. we can measure the ‘renal clearance’ of a drug

Question 3

What are the two important renal examples of clearance?

Answer 3

renal clearance of creatinine = GFR
- because any creatinine contained in the filtered volume will be completely cleared by the kidneys
renal clearance of PAH = RPF
- because any PAH in the plasma that reaches the kidney will be cleared from the body

Question 4

What is the clearance equation?

Answer 4

Clearance = (urine conc x flow) / plasma conc

Question 5

What is most likely explanation for the following renal clearances:

1. 0
2. GFR
3. =RPF
4. > RPF

Answer 5

1. Neither filtered noe screted (e.g. large proteins)
2. Filtered, then partially reabsorbed
3. Filtered, but not reabsorbed
4. Filtered, and partially secreted
5. Filtered and secreted
6. Production in the kidney

Question 6

What is whole body clearance?

How is it easily measured?

Answer 6

• the sum of the individual organ clearances, but this is rather hard to do
• measure how the concentration of the substance changes over time. This I sthe method by which pharmaceutical companies measure clearance of drugs during clinical trials (Phase 1)

Question 7

On a conc over time graph of a drug, what part of the graph represents clearance?

Answer 7

the area under the curve represents the clearance of the drug

Question 8

What pharmacokinetic model does clearance usually follow?

Answer 8

first order clearance

e.g. the substance is removed at a rate proportional to the conc in the body

Question 9

How do you calculate the halflife of a drug?

Answer 9

ln(2) / k

k= the rate constant

Question 10

How are k, volume of distribution and clearance related?

Answer 10

Cl = k x Vd

Question 11

What’s the use of k, Vd and Cl?

Answer 11

the aim of measuring and understanding these parameter is to be able to predict and simulate how the concentration of hormones, drugs and other substances will change in the circulation over time
- if the need arises, Vd for a given patient can be calculated, clearance can be estimated and hence the change of drug level predicted over time