||Section 1 - Pharmacokinetic Concepts|
The basic goal of therapeutic drug monitoring (TDM) is to enhance the patient's chance of maximum benefit from a prescribed drug while minimizing the risks of toxicity. Characteristics of drugs associated with TDM are:
As successive doses are administered, drug begins to accumulate in the body. With first order elimination, at a certain point in therapy, the amount of drug administered during a dosing interval exactly replaces the amount of drug excreted (rate in = rate out). When this equilibrium occurs, the peak and trough drug concentrations are the same for each additional dose given. When peak and trough concentrations are the same with two or more successive doses, steady-state is reached.
The time required to reach steady-state is approximately 4 to 5 half-lives.
You should note from this graph that failure to evaluate steady-state levels can lead to significant errors in estimates of elimination rate and in prediction of the appropriate dosage. Therefore, serum sampling is best performed at steady-state.
Timing serum level draws
Serum samples must be drawn during the elimination phase, when net distribution is complete.
You should note from this graph that failure to consider the distribution phase can lead to significant errors in estimates of elimination rate. An accurate measure of Kel can only be obtained when serum levels are drawn in the elimination phase.
Please be aware of the widespread policy of nursing personnel to record a dose
as having been given exactly as ordered if it is given within 30 minutes of the
recorded time. This will lead to significant errors in analysis, therefore,
you must confirm all times, including infusion times.
The length of infusion has a significant effect upon the peak serum level. If we were to administer the same dose to the same patient at different infusion rates, the peak levels would differ significantly:
You should note from this table that failure to use the actual infusion time can lead to significant errors in estimates of Vd and elimination rate.
Please be aware of the widespread policy of nursing personnel to record a dose as having been given exactly as ordered if it is given within 30 minutes of the recorded time. This will lead to significant errors in analysis, therefore, you must confirm all times, including infusion times.
Other TDM Precautions
Always rule out errors before accepting out of range data. Common pitfalls and potential sources of error (in decreasing order of likelihood) are:
To help visualize these pharmacokinetic concepts, I've created a little program called KinPlot. You enter the model parameters and dosage regimen and the program displays the resulting serum level plot. You may compare up to six different dosing regimens on one screen, varying the dose, interval, infusion time and starting level so that you can how these affect serum levels.
Section 1 - Pharmacokinetic Concepts
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