Hepatic Clearance Flashcards Preview

Pharmacokinetics and Biopharmaceutics > Hepatic Clearance > Flashcards

Flashcards in Hepatic Clearance Deck (12):
1

What are two major determinants of hepatic clearance?

  • Efficiency of drug removal
  • Efficiency of blood delivery to the liver

2

What is hepatic clearance due to?

  • Hepatic clearance is typically due to metabolism, although in some very uncommon cases this could be excretion into the bile (I would call this billiary clearance and NOT hepatic clearance though)

3

What is hepatic clearance?

  • Hepatic clearance is usually assumed to be the clearance of a drug that is not renal:
    • CLH = CL - CLR

4

If there are other clearance pathways what is the equation?

  • CLH = CL - CLOTHER   - CLR

5

What is the Hepatic Extraction Ratio and what affects this ratio?

  • The fraction of drug entering liver in the blood which is irreversibly removed during one pass of the blood through the liver
  • Affected by
    • liver blood flow (QH)
    • Fraction of drug unbound in plasma (fu)
    • Metabolic capacity of the liver (CLint) for the drug
  • CLHb   = CLH / λ

6

Hepatic clearance is influenced by?

hepatic extraction ratio of the liver for a drug and liver blood flow (EH x QH)

7

Hepatic extraction ratio (EH)  is also the determinant of what?

of first-pass extraction during the "first-pass effect" (1-EH)

8

EH = CLHb / QH

If EH is high (>~0.7), then

  • CLH is only affected by changes in QH
  • The first-pass effect component of bioavailability after an oral dose is affected by changes in QH, fu and CLint

9

EH = CLHb / QH

If Eis low (

  • CLH is only affected by changes in fu and CLint
  • The first-pass effect component of bioavailability after an oral dose is relatively unaffected by changes in any of the factors in QH,  fu and CLint

10

What is intrinsic clearance?

The intrinsic ability of the liver to remove (metabolise) the drug in absence of restrictions imposed on drug delivery to the liver cell by blood flow or protein binding

11

If Clint for drug is high?

Its metabolism by the liver is limited by hepatic blood flow

12

If Clint for drug is low?

Hepatic blood flow will have minimal influence on its metabolic rate