Formula for Hepatic Drug Clearance

750HepaticClearance.GIF

  • Qh = Hepatic Blood Flow

  • Fp = Fraction Unbound in the plasma

    • only unbound fraction can be metabolized
  • Cli = Intrinsic Clearance of the drug
Extraction Ratio
  • E = (Cin-Cout)/Cin
Ranges of Extraction Ratio
  • Low < 0.2
  • Intermediate 0.2 - 0.8
  • High > 0.8
How dose extraction ratio affect Hepatic Clearance
  • High Extraction ratio drugs

    • Cli >> Qh
    • when clearance is significantly greater than blood flow, the dominant factor becomes clearance
    • There is always enough drug for the liver to process, a lot of blood or a little blood makes very little difference
    • High extraction ratio drugs are relatively unaffected by CHF, but are heavily influenced by Liver Disease
    • Clh ~ Cli
  • Low Extraction ratio drugs

    • Qh >> Cli
    • when clearance is significantly smaller than blood flow, the dominant factor becomes intrinsic clearance
    • The lobules can't grab much drug from the blood, so they need exposure to a lot of drug
    • Clearance is affected by both CHF and Liver Disease
    • Clh ~ Cli * Fp
Factors Reducing Hepatic Clearance
  1. CHF

    • Reduced blood flow
    • Especially true for low extraction ratio drugs
    • Increased plasma concentration of drug which are metabolized in the liver or have a high first pass effect
  2. Cirrhosis

    • Increased plasma concentration due to reduce hepatocyte function
  3. Binge drinking

  4. Alcoholism

    • Decreased plasma concentration due to hyperactivity of the liver
    • Switches when cirrhosis kicks in
  5. Overeating

    • Reduces cardiac output
  6. Intense Exercise

    • Damned if you do, damned if you don't
    • ToDo
Examples of drugs affected by altered Hepatic Clearance
Factors Increasing Liver Function
  1. Smoking Nicotine

  2. Smoking Cannabinoids
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