The three compartment model

Three Compartment Model

• A three-compartment model is commonly used to describe the pharmacokinetics (PK) of intravenous drugs
• After an IV bolus, the plasma concentration peaks and then exhibits an exponential decline that follows 3 distinct phases
  • Initial rapid drop
  • The rate of decrease then slows
  • Finally, there is a steady and predictable decrease
• This can be explained by the movement of the drug between a central (V1) and 2 peripheral compartments (V2 & V3)
• These are not distinct anatomical compartments
  • V1 is the central compartment which equilibrates with the effect site (brain) and from which the drug is removed from the body (e.g. liver metabolism and renal excretion)
  • V2 and V3 represent “reservoirs” where the drug moves from V1 and which have no connection with the effect site. V2 (mostly muscle) is better perfused than V3 (fat and bone) but has a smaller capacity to absorb drugs than V3
• The movement of the drug between compartments is dynamic (in and out according to the concentration gradient) and can be described by an equilibration constant between each compartment
• The central compartment (V1) is connected to the effect site whereas the peripheral compartments (V2 and 3) have no direct connection to the effect site

Hydraulic Model

• The movement of drugs between compartments can be illustrated using a “hydraulic” model which is an easier way to conceptualize the movement of drugs between compartments. The size of the pipe reflects the speed of drug movement and the size of the container, the capacity to hold the drug e.g. V2 is a fast transfer compartment with a smaller capacity than V2, which is slower to fill.
• The clinical effect of an intravenous anaesthetic relies on the action of the drug on the receptor(s) in the bio-phase (brain), also called the effect site
• The drug’s “effect” depends on the concentration in the effect site (surprise!) which, in turn, depends on the concentration in the central compartment (V1) and how quickly it can equilibrate (cross the blood-brain barrier)