3. Old stuff
          3.1. Old pharm stuff (pre 2009)
              3.1.3. Pharmacology
                  3.1.3.1. Pharmacology principles
                      3.1.3.1.1. Pharmacokinetics
 3.1.3.1.1.4. Clearance 

Clearance

[SH4:p13]

  • Clearance 
    = the volume of plasma cleared of drug PER UNIT TIME
    * By renal excretion and/or metabolism in liver or other organs

 

Non-organ clearance

  • e.g. Hofmann elimination and ester hydrolysis
  • Responsible for clearance of succinylcholine, atracurium, cisatracurium, and mivacurium

Hepatic clearance

  • Product of hepatic blood flow and hepatic extraction ratio
    * i.e. Hepatic clearance = HER x HBF

Perfusion-dependent elimination

High hepatic extraction ratio (>0.7)

  • Clearance more depends on the blood flow
  • Changes in enzyme level have minimal influence
  • e.g. fentanyl, sufentanil

Capacity-dependent elimination

Low hepatic extraction ratio (<0.3)

  • Clearance more depends on the enzyme activity or protein-binding
  • Changes in blood flow have minimal influence
  • e.g. alfentanil

Biliary excretion

  • Most metabolites produced by liver are excreted in bile
    --> Enter GIT
    --> Reabsorbed into circulation
    --> Eliminated in urine

Renal clearance

Water-soluble compounds are excreted more efficiently
--> Less reabsorption in the tubules

Renal clearance depends on:

  • Glomerular filtration
    * Influenced by GFR and protein binding
  • Active tubular secretion
  • Passive tubular reabsorption
    * Reabsorption is high for lipid-soluble drugs
    * pH influences the fraction that is ionised, thus not absorbed

NB:

[???] (Need verification) From James' notes:

  • Drugs largely excreted unchanged in urine (75-100%) include:
    * Frusemide
    * Gentamicin
    * Atenolol
    * Ampicillin
    * Digoxin