L09-The concept of clearance

Question 1

What is renal clearance?

Answer 1

Volume of body fluid cleared of a substance per unit time.

Question 2

How can you calculate the renal clearance of a drug by urine samples and plasma concentrations?

Answer 2

clearance is equal to the (concentration of the drug in the urine times the volume produced per unit time)/ Concentration of the drug in the plasma.

Cl=Cu(V/T)/Cp

Question 3

• Typically, the excretion rate for Na+,
is around 100 µmol.min-1.
Given a plasma Na+ concentration of 140
mM=140µmol.ml-1
What is the renal clearance?

Answer 3

(100 µmol.min-1)/(140µmol.ml-1)=0.7ml.min-1

Question 4

What does it mean if renal clearance equals 0?

Answer 4

Then the substance is neither filtered nor secreted or all of the substance that is filtered is reabsorbed

Question 5

What does it mean if renal clearance is less than GFR?

Answer 5

Then the substance is partially reabsorbed

Question 6

What does it mean if renal clearance equals GFR?

Answer 6

Then the substance is filtered but not reabsorbed

Question 7

What does it mean if renal clearance is greater than GFR but less than RPF?

Answer 7

Then the substance is filtered and not reabsorbed aswell as being partially secreted

Question 8

What does it mean if renal clearance equalls RPF?

Answer 8

Then the substance is filtered and not reabsorbed and secreted

Question 9

What does it mean if renal clearance is greater than RPF?

Answer 9

The substance is produced in the kidney

Question 10

How can whole body clearance be measured?

Answer 10

The plasma concentration of the substance can be measured over time.

Question 11

When excretion rate cannot be measured how is clearance measured?

Answer 11

clearance=dose/area under the curve

Area under the curve is from a concentration vs time graph

Question 12

What is the equation for working out concentrations?

Answer 12

C=Cmaxe^-kt

Question 13

What is the half life equation?

Answer 13

t1/2=ln(2)/k

Question 14

What is the concentration equation in terms of half lives?

Answer 14

C=Cmax(1/2)^number of half lives

Question 15

What is the clearance equation in terms of volume of distribution?

Answer 15

Cl=kVd

Question 16

Mr BV is a 48 year old man being treated or H
influenzae pneumonia with cefuroxime. His history is
notable the loss of his spleen and one kidney in a
MVA (aged 19); he weighs 75kg. He was advised to
take 500mg cefuroxime orally, twice a day, and
being a keen mathematician he decided to work
out how many tablets he needed himself. He
manage to take 5000mg instead (powers of 10
weren’t his strong point). His renal clearance is
measured as 100ml.min-1. He was advised to stop
taking the antibiotic, but how long should he wait
before resuming? What if his GFR was 10ml.min-1?
Oral bioavailability 32%
• Almost 100% renally cleared
• Cefuroxime Clearance=Creatinine clearance
• Vd=0.2 L.kg-1
• Usual peak at 2-3 hours post-dose, due to the time taken
for absorption (but ignore this for the initial calculation)

Answer 16

Absorbed Dose= Dose X Bioavailability = 0.5 X 0.32 = 0.16g
Vd(L)=Vd (L.kg-1) X Mass (kg)= 0.2 X 75 = 15L
Cl (L.hour-1) = Cl (L.min-1) X 60(min.hr-1) = 0.1 X 60 = 6L.hr-1
Assuming ‘instant’ absorption, the peak concentration can be found using:
Cpeak= (Absorbed Dose)/Vd = 0.16/15 = 0.011g.L-1
We can find the rate constant k using:
k=Clearance/Vd= 6/15 = 0.4hr-1
We can then describe the concentration (C) over time(t) by:
C=Cmaxe^-kt

Question 17

What is the equation for the rate of excretion?

Answer 17

rate of exretion=-kC

where C is concentration