FRCA Notes

Types of Pharmacokinetic Models

  • Pharmacokinetic models allow predictions of drug behaviour in the body based on mathematical models, with greater accuracy than assuming the body is a single container
  • They can be classified as either:
    • Compartment models (the most common)
    • Non-compartment models
    • Physiological models
  • A compartment is: one or more components of a mathematical model that aim to replicate the drug-handling characteristics of a portion of the body
  • Pharmacokinetic models can contain any number of compartments
    • Typically, one-compartment modelling is too inaccurate for studying pharmacokinetics
    • Three-compartment modelling is accurate enough without being overly complex

Types of compartment modelling

  • Mamillary modelling is where there is a central compartment to which a stated number of peripheral compartments are connected
  • This is the most commonly used method

  • Catenary modelling is where each compartment is connected in a linear chain; each compartment only links with its immediate neighbour

  • Non-compartmental models make no assumption about specific volumes
  • They use information from the area under the concentration-time curve, as this represents removal of the drug from the plasma

Clearance in non-compartment models

  • The area under the concentration-time curve (AUC) for a drug is the ratio of the dose given to the clearance of the drug
  • I.e.  AUC = dose / clearance
  • This can be rearranged to show:

    • Cl = dose / AUCIV

  • This only works for IV administrations as the bioavailability is 1, for oral drugs:

    • Cl = (dose x bioavailable fraction) / AUCPO

Moment curve

  • The first moment curve is a graph of concentration multiplied by time (y-axis) against time (x-axis)
  • The area under the first moment curve (AUMC) can be used to find the mean residence time (MRT, measured in minutes)
    • The mean residence time is a measure of how long a drug stays in the body
    • It is similar to the time constant in compartmental models
    • It is dependent on lipid solubility, among other factors

    MRT = AUMC / AUC


  • The product of clearance (ml/min) and MRT (min) is the volume of distribution at steady state, i.e.:

    • VDss = MRT x Cl