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Section 1 - Pharmacokinetic Concepts

Therapeutic drug monitoring

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:


Steady state
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.

SS plot


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.

2-comp plot


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.


Infusion length
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:

Infusion Dose Interval Peak level
30 min 500 mg 8 hrs 26.8
60 min 500 mg 8 hrs 25.3
120 min 500 mg 8 hrs 22.5


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:

  1. Administration times not recorded accurately.
  2. Dose administration error.
  3. Blood drawn at incorrect time.
  4. Blood drawn before steady-state.
  5. Blood drawn from wrong site.
  6. Lab assay error.
  7. Pharmacy dispensing error.


KinPlot
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.


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Section 1 - Pharmacokinetic Concepts

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