FRCA Notes

Clearance and Elimination

  • Clearance is the volume of plasma from which a drug is completely removed per unit time
  • It is measured in ml/min and abbreviated to Cl
  • Clearance gives a value for the volume of plasma cleared of a drug, but does not dictate the mechanism by which this occurs (can be metabolism, distribution or excretion)
  • It is usually constant over the therapeutic range for a given drug (i.e. describes elimination in first order kinetics)

Routes of clearance

  • Systemic clearance is the sum of the elimination that is undertaken by each organ:

    • Clsystemic = Clrenal + Clhepatic + Clother

  • Typically the kidneys and liver play a prominent role, but other organs such as the lungs (volatiles), muscles (remifentanil) and plasma (suxamethonium, atracurium) are involved

Calculating clearance

  • In general, clearance is calculated using a non-compartmental model: Cl = dose ➗ AUC

    • Clearance = dose ➗ area under concentration-time curve


  • An organ's clearance of a drug can also be described as: Cl = Q.ER

    • Clearance = Organ blood flow x drug extraction ratio

Unicompartmental clearance

  • In a simple one-compartment model, clearance is the product of the volume of distribution and the rate constant for elimination:

    • Cl = k.VD

  • Knowing that:
    • The rate constant for elimination is inversely proportional to the time constant (k = 1/𝛕)
    • And that half-life is equal to ln(2) of 𝛕 (t1/2 = 0.693.𝛕)
  • One can describe clearance in terms of volume of distribution and half-life:

    • Cl = VD.(0.693➗t1/2)

Multi-compartmental clearance

  • In a multi-compartment model, there are inter-compartmental clearances as well as clearance from the body (elimination)
  • As such, clearance from the body is the product of the rate constant of elimination (k10) and the volume of the central compartment (V1)
  • In practice this means drugs with vastly different volumes of distribution and rate constants of elimination can have similar clearance

  • Elimination describes the removal of a drug from the plasma
  • It is comprised of both distribution and metabolism
  • The rate of elimination is a product of clearance and concentration: Relim = C.Cl
  • Note this is the same as the required rate of infusion to maintain a plasma concentration in a one-compartment model
  • Elimination can also be described in terms of volume of distribution and rate constant for elimination:

    • Relim = kelim.VD