Renal Clearance Flashcards Preview

Pharmacokinetics and Biopharmaceutics > Renal Clearance > Flashcards

Flashcards in Renal Clearance Deck (15):
1

How can an unchanged drug be excreted in the urine?

  • The only way that unchanged drug can be excreted in the urine is if it is cleared by the kidneys
    • The fraction of the dose which is excreted in the urine as unchanged (ie. un-metabolised) drug corresponds to the proportion of total CL that is due to renal clearance

2

Renal clearance can easily be calculated if one knows the fraction of the dose that is excreted in the urine as unchanged drug (fe) and total clearance, what is the formula?

CLR = CL x fe

3

fe can be calculated from the amount of drug excreted unchanged in the urine (Ae) and the dose, what is the formula?

fe = Ae/D

4

What 3 Mechanisms are involved in Renal Clearance?

  • Filtration
  • Secretion
  • Reabsorption

5

Describe Filtration

  • Filtration of drug that is not bound to plasma proteins (ie. the filtration component of renal clearance)
  • Unbound drug is filtered at the glomerulus along with water.  Approximately 120mL/min of water is filtered (GFR) in a healthy adult
    • Thus, the filtration component of renal clearance is calculated as fu x GFR.

6

Describe Secretion

  • Drug may also be secreted into the lumen of the renal tubule via active transport
  • This must be an active process as the drug is concentrated in the filtrate as water is reabsorbed back into the body as part of normal homeostasis
    • As a result the drug concentration in the filtrate is greater than in the blood

7

Describe Reabsorption

  • Once drug is filtered / secreted it may be reabsorbed back into the blood - this will decrease the amount of drug excreted by the kidneys.
  • This is typically a passive process because, as above, the drug concentration in the filtrate is greater than in the blood, ie a concentration gradient exists favouring movement out of the tubule back into the blood
  • For reabsorption to occur the drug must be sufficiently lipophillic to cross the membrane barrier presented by the tubule membrane

8

If renal clearance is greater than the filtration component (fu x GFR) ....

  • then there must be overall net secretion (as more drug is excreted than was filtered alone)
  • reabsorption may be occuring but, if it is, its -ve contribution is less than the +ve contribution from CLRS

9

If renal clearance is smaller than the filtration component (fu x GFR)...

  • then there must be over all net reabsorption (as more drug is excreted than was filtered alone)
  • secretion may be occuring but, if it is, its +ve contribution is less than the -ve contribution from reabsorption

10

There are a series of consequences of the reabsorption process if the drug undergoes overall net reabsorption: Changes in urine pH may affect the ionisation of the drug

  • Thus if the change in pH causes a greater proportion of the drug to be unionised, then reabsorption will increase --> decreased renal clearance
  • Conversely, if the change in pH causes a smaller proportion of the drug to be unionised then reabsorption will decrease --> increased renal clearance

11

There are a series of consequences of the reabsorption process if the drug undergoes overall net reabsorption: Changes in urine flow rate may affect reabsorption

  • If urine flow rate increases (ie diurises) then the concentration gradient favouring movement out of the tubule back into the blood will be reduced
    • Thus reabsorption will decrease, and renal clearance will increase
  • Conversely if urine flow rate decreases (perhaps due to dehydration) then the concentration gradient favouring movement out of the tubule back into the blood will be increased
    • Thus reabsorption will increase, and renal clearance will decrease

12

There are a series of consequences of the secretion process if the drug undergoes overall net secretion, as this is an active process carried out by specific transport proteins: There is a degree of specificity in the affinity of a drug for a specific transporter

Thus the secretion of a drug may be reduced by competition with another drug that the patient may be consuming if they are both secreted by the same transporter.

13

There are a series of consequences of the secretion process if the drug undergoes overall net secretion, as this is an active process carried out by specific transport proteins: The transport system may have different capacity to secrete any given drug

The transport system may have different capacity to secrete any given drug, and this may vary from drug-to-drug even if they are secreted by the same transporter.

14

There are a series of consequences of the secretion process if the drug undergoes overall net secretion, as this is an active process carried out by specific transport proteins: Potentially Saturable

The transport system will have limited capacity to secrete any given drug - it is potentially saturable.  Thus saturation of secretion may result in decreased renal clearance at higher doses

15

If urine flow rate is increased (i.e. less water is being reabsorbed)...

Then the drug concentration gradient will be decreased and therefore less tubular reabsorption of drug will occur and total CLR will increase