      Section 1 - Pharmacokinetic Concepts

### Pharmacokinetic modeling

Pharmacokinetic models are relatively simple mathematical schemes that represent complex physiologic spaces or processes. Accurate PK modeling is important for precise determination of elimination rate.

The most commonly used pharmacokinetic models are:

• 1-compartment
• 2-compartment

One compartment model
All drugs initially distribute into a central compartment (Vc) before distributing into the peripheral compartment (Vt). If a drug rapidly equilibrates with the tissue compartment, then, for practical purposes, we can use the much simpler one-compartment model which uses only one volume term, the apparent volume of distribution, Vd. Example
The distribution phase for aminoglycosides is only 15-30 minutes, therefore, we can use a one-compartment model with a high degree of accuracy.

Serum level plot for a 1-compartment model

Yields a straight line when using a log scale on the y-axis. Two compartment model
Drugs which exhibit a slow equilibration with peripheral tissues, are best described with a two compartment model. Example
Vancomycin
is the classic example, it's distribution phase is 1 to 2 hours. Therefore, the serum level time curve of vancomycin may be more accurately represented by a 2-compartment model.

Serum level plot for a 2-compartment model

Yields a biphasic line when using a log scale on the y-axis. Distribution phase
During the initial, rapidly declining distribution phase, drug is moving from the central compartment to the tissue compartment.

Elimination phase
Elimination of drug is the predominant process during the second phase of the biphasic plot. Because elimination is a first-order process, the log plot of this phase is a straight line. You should also note from this graph that failure to consider the distribution phase can lead to significant errors in estimates of elimination rate and in prediction of the appropriate dosage. This is especially important with vancomycin. Unless you are using a two-compartment model, you should not use a level drawn during the distribution phase to calculate the elimination rate.

Summary

• A one-compartment model may be used for drugs which rapidly equilibrate with the tissue compartment, e.g, aminoglycosides.
• A two-compartment model should be used for drugs which slowly equilibrate with the tissue compartment, e.g, vancomycin.
• A log scale plot of the serum level decay curve of a 1-compartment model yields a straight line.
• A log scale plot of the serum level decay curve of a 2-compartment model yields a biphasic line.
• Failure to consider the distribution phase can lead to significant errors in estimates of elimination rate.      Section 1 - Pharmacokinetic Concepts