Biv: Describe drug clearance, its determinants and how it is estimated

Definition

  • Clearance = the amount of plasma cleared of drug per unit time (mL/min)
  • Only applies 1st order kinetics
  • It is a constant which relates the rate of elimination to Cp

RATE OF ELIM = CLEARANCE x Cp

    • Allows calculation of dose interval

CLEARANCE (total) = Cl (hepatic) + Cl (renal) + Cl (other)

Cl (Hepatic)

  • Determined by HBF x HER
  • Low ER → depends on intrinsic clearance & PPB
  • High ER → depends on HBF

Cl (Renal)

  • Mainly excretion of drug unchanged in urine
  • Depends on GFR (PPB), reabs (passive), secretion (active)

Cl (Other)

  • Plasma esterases
  • Hoffman elimination
  • Lung metabolism

Determining Clearance

Determining Clearance
  • t ½ & Vd
Clearance