FRCA Notes

Three Compartment Model

  • Most anaesthetic drugs are accurately modelled using three compartment models
  • Commonly used TCI models are three compartment models, and target set plasma concentration
    • Some models allow effect-site targeting e.g. Eleveld, modified Marsh
  • However, the clinical effects of drugs used in TCI is via their effect on the brain
  • The 'effect' (brain) compartment is thus considered to be a separate compartment
  • It is in equilibrium with the central compartment, but with a lag-time to account for blood-brain equilibration
  • There is an elimination rate constant from the effect compartment (ke0) and a half life for equilibration (t1/2ke0)

Three compartment model

Adapted from Physics, Pharmacology and Physiology for Anaesthetists

  • Where:
    • C0 = 'outside compartment'
    • C1 = central compartment
    • C2 = peripheral compartment [representing less vascular tissues of the body]
    • C3 = peripheral compartment [representing the least vascular tissues of the body]
    • Rate constants for drug movement between all the different compartments are present
    • The volume of distribution at steady state is the sum of the volumes of the three compartments

  • As drug enters the central compartment, it is distributed along prevailing concentration gradients:
    • Rapidly to the second compartment
    • Slowly to the third compartment

  • Peripheral compartments may act as reservoirs, keeping the drug concentration in the central compartment steady even as elimination occurs
  • The ratio of the rate constants from the central to peripheral compartments therefore affects how quickly a drug will be fully eliminated
  • Elimination still only occurs from C1

  • A semi-logarithmic graph of ln(concentration) vs. time for a three compartment model is a tri-phasic exponential decay curve
two compartment model graph

Adapted from Physics, Pharmacology and Physiology for Anaesthetists


  • As before:
    • Line a represents distribution to rapidly equilibrating tissues
    • Line c represents distribution to slowly equilibrating tissues
    • Line b represents terminal elimination from the body
    • C0 = A + B + C

Ct = A.e-ɑt + B.e-βt + C.e-ɣt

  • The term C.e-ɣt represents the distribution to slowly equilibrating tissues
  • The term B.e-βt represents the terminal elimination phase