Clearance

[Ref: SH4:p13]

Clearance - the volume of plasma cleared of drug by renal excretion and/or metabolism in liver or other organs.

 

Nonorgan 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

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