| Section 1 - Pharmacokinetic Concepts |
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:
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
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
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
| Section 1 - Pharmacokinetic Concepts |