Three different compartment models to understand drug pharmacokinetics & elimination
Single Compartment Model
Where there is theoretically a single compartment of distribution
The single compartment is the intravascular volume
Characterised by a distribution volumeYou would need to consider bolus, infusion and extra-vascular doses
Not really considered much any more, due to the lipid solubility and movement of a lot of drugs into different tissues in the body.
Once a dose reaches peak conc (C0), the process of clearance is exponential.
Two Compartment Model
Tissues, into which the drug distributes more slowly, are lumped together as one peripheral compartment. The drug enters and leaves the peripheral from the central at a rate depending on transfer rate constants.
The transfer from the central compartment to the peripheral compartment can be quite fast, and the corresponding rapid decrease in the drug plasma concentration is called the distribution phase. CENTRAL = RAPID EQUILIBRIUM, PERIPHERAL = SLOW EQUILIBRIUM
The second phase is the elimination phase, which is longer, because the drug must first diffuse back from the peripheral compartment to the central compartment in order to be eliminated.
(C0), = back-extrapolated plasma drug concentration at time zero following bolus intravenous injection as if distribution was immediate.
Three Compartment Model
- This now includes vessel rich and poor groups.
- Better explains the quicker distribution to vessel rich tissue like viscera and muscle compared to poorer fat.
- Most anaesthetic agents follow this model, going to muscle first, then fat.
- Movement between compartments is dependent on the concentration gradient between them and so
slows down when more drug accumulates in the poorer tissues.
K01 = constant of moving from compartment 0 (outside) to C1
K10 = constant of elimination. C1 = central compartment
A semi-log plot of drug concentration versus time will no longer be linear as the drug has two possible paths to move along, each with their own associated rate constants.
1 = Distribution to vessel rich
2 = Distribution to vessel poor
3 = Elimination
These peripheral compartments may act as reservoirs keeping the central compartment full even as elimination is occurring from it.
Elimination always occurs from the central compartment
Dr. David Lyness
The 'K' numbers describe movement from compartments (as a constant)
such as K01 really means K, compartment 0 moving to compartment 1 etc.
0 compartment is the drug outside the body!