The concept of clearance L09

Question 1

Define clearance

Answer 1

the volume of body fluid cleared of a substance per unit time

Question 2

What units are used for clearance?

Answer 2

ml/min or L/hr

Question 3

What measurement is the renal clearance of creatinine equal to?

Answer 3

GFR - freely filtered and all of the creatinine in filtrate will be cleared in urine

Question 4

What measurement is the renal clearance of PAH equal to?

Answer 4

RPF - any PAH in plasma that reaches kidney will be cleared from the body.

Question 5

What is the equation for renal clearance of random substance ‘x’?

Answer 5

Clx = (Cx,u x Vdot)/Cx,p = excretion rate/Cx,p

where Cx,u = urinary concentration of x
Cx,p = plasma concentration of x
Vdot = urine flow rate

Question 6

If Clx = 0, what can be implied about the excretion of x?

Answer 6

x is neither filtered nor secreted e.g. large plasma proteins

Question 7

If Clx < GFR, what can be implied about the excretion of x?

Answer 7

x is filtered and then partially reabsorbed e.g.Na+

Question 8

If Clx = GFR, what can be implied about the excretion of x?

Answer 8

x is filtered and not reabsorbed e.g. creatinine

Question 9

If Clx > GFR and < RPF, what can be implied about the excretion of x?

Answer 9

x is filtered and partially secreted

Question 10

If Clx = RPF, what can be implied about the excretion of x?

Answer 10

x is filtered and secreted e.g. PAH

Question 11

If Clx > RPF, what can be implied about the excretion of x?

Answer 11

x is produced in the kidney

Question 12

What method is used to measure whole body clearance?

Answer 12

measure how the concentration of a substance (drug) changes over time.

Question 13

How can clearance be calculated from a graph showing changes in drug concentration over time?

Answer 13

Clearance = dose of drug/AREA under curve

*therefore if area is large > low clearance
if area is small > high clearance

Question 14

What equation represents how the concentration of a drug changes over time in the body?

Answer 14

C = Cmaxe^-kt

C = concentration
Cmax = maximum concentration of drug in the body (when first administered)
e = exponential decline of drug
k = rate constant
t= time

Question 15

How do you calculate the half life of a drug?

Answer 15

t1/2 = ln(2)/k

where k=rate constant

Question 16

How can you calculate the concentration of drug in the body at a given time using half-lives rather than ‘e’?

Answer 16

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

where Cmax = maximum concentration of drug in the body

Question 17

State an equation relating clearance, the rate constant and the volume of distribution.

Answer 17

Cl = k x Vd

Question 18

What is cefuroxime?

Answer 18

antibiotic used in treatment of urinary, skin and lower respiratory tract infections.

Question 19

What is the oral bioavailability of cefuroxime?

Answer 19

32%

Question 20

What is the renal clearance of cefuroxime?

Answer 20

almost 100% *same as creatinine clearance

Question 21

What is the volume of distribution of cefuroxime?

Answer 21

0.2L/kg

Question 22

NOTE

Answer 22

look at graphs in lecture handout showing variation in cefuroxime concentration over time depending on doses and also in circumstances of renal failure

*main message - in a healthy patient, cefuroxime will be fully cleared from the body in a certain amount of time (around 10 hours) no matter how high the dosage is.

In patients with renal failure, the drug cannot be fully cleared from body as kidneys only have 10% of their normal function so drug remains within circulation and fluctuates in concentration as more doses are given.