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