Bi: Explain the concept of pharmacokinetic modelling of single and multiple compartment models

  • PK compartment = mathematical concept describing a space in the body the drug is occupying – it does not correspond to anatomy/volume
    • Compartment models work by dividing the body into a number of hypothetical compartments
    • NB: these are all mathematical concepts, there is no anatomical equivalent
    • They are used to help us understand the ∆ plasma [ ] of a drug over time

One Compartment Model

  • Assumes body is one homogenous unit
  • Drug is given & achieves instant distribution throughout body & equilibrates instantly b/w tissues

INPUT (dose) → [DRUG IN BODY] → OUTPUT (elimination)

  • Drug is then eliminated in a [ ] dependent manner (exponentially)
CP

Cp = C0e-kel.t

Cp = [  ] plasma at time (t)

CP1

= rate constant

i.e. 0.5 = 50% removed per unit of time

Linear Model

Graphically displays as a linear model

Highly hydrophilic drugs – AMINOGLYCOSIDES – follow this model because they are confined to ECF & have poor tissue penetration

Two Compartment Model

  • Central compartment = plasma
  • Peripheral compartment = tissues
  • Drug enters K01 central compartment
  • Drug eliminated K10 central compartment
  • From central compartment drug redistributes to peripheral compartment K12
  • Drug cannot be eliminated from peripheral compartment, must return to central compartment K21
  • When drug administered to central compartment there is a rapid decline in [ ] due to K12
  • K12 continues until equilibrium b/w both compartments
  • Then drug is eliminated K10
  • As that happens drug will move K21 down its [ ] gradient to then be eliminated K10
LogCP

logCp vs time is used to distinguish from 1 compartment model

  • α = initial rapid decline, distribution from Central → Peripheral compartment
  • β = elimination from central compartment
    • ∴t ½ α = distribution half life
    • ∴t ½ β = elimination half life

Propofol & 2 Compartment Model

  • After initial induction dose 1.5 – 2.5mg/kg, there is rapid LOC → drug taken up by lipophilic CNS tissues
  • The PPF distributes to peripheral tissues, Ph 1 at constant rate α
  • If another dose isn’t given, patient will wake up
  • If a continuous infusion is given, the peripheral compartment will become saturated with PPF

Multicompartment Model

  • Drug distributes >1 compartment
  • logCp vs time shows >1 expotential
  • Drug administered
  • Rapid distribution phase
  • Second slower distribution phase
  • Elimination phase