Practical considerations for therapeutic drug monitoring

Therapeutic drug monitoring (TDM) is the measurement of the concentration of specific drugs at intervals in order to adjust dosage regimens to achieve a desired clinical effect and avoid toxic effects.

TDM is used where:

1. There is an established relationship between blood drug concentration and therapeutic response and/or toxicity
2. There is a poor relationship between blood drug concentration and drug dosage
3. There are clear clinical indications for the test (such as: no response to treatment; suspected non-compliance; signs of toxicity)
4. The specimen can be provided, appropriately timed and dated, with identifiable patient information
5. Adequate clinical information is supplied to allow the interpretation of results

In order to get meaningful results when undertaking therapeutic drug monitoring, the following needs to occur:

• All dosing and collection time details should be included on the request from (see Table 1)
• Samples should not be collected until drugs have reached steady state (five half lives) (see Table 2)
• Bloods should be collected at the recommended sampling time (see Table 2)

The timing of blood collection is important

Sample once steady state achieved

In most cases blood samples should not be collected until concentrations have reached steady-state. This occurs when the rate of drug administration and drug elimination are equal, for most drugs this is achieved after 4–5 half-lives. If a loading dose has been administered, steady state may be achieved earlier. Drug concentrations may be determined earlier if toxicity is suspected. It is important to wait for steady-state both at initiation and following any dosage change.

Sample at the appropriate time in relation to last dose

When a drug is administered, it goes through the stages of absorption, distribution, metabolism and elimination. Drug concentrations are generally measured in the elimination phase (correlates with trough) as this gives a more predictable and reliable guide to drug dosing.

Different drugs have variable pharmacokinetic characteristics, for instance, digoxin and lithium have extended distribution phases following dosing. This means, that if blood is taken too soon after administration, the level will appear to be elevated.

Details to include on the request form

Table 1: Information required on request form¹

To accurately interpret results, it is important the request form contains all relevant information. See Table 1.

It can be difficult to make sense of a result unless collection time and previous last dose is known. For example, drug levels that are in the toxic range may have been taken only a few hours post dose, and therefore the drug was still in its distribution phase.

It is important to note how long the person has been on the drug, to ascertain they have achieved steady-state. If there are any known issues with compliance, include on the form.

It is also useful to include on the request form any co-morbidities or other medications, as these may effect the drug pharmacokinetics. For example, steady-state for digoxin is 5–7 days, but may take up to three weeks in a person with renal failure.

Table 2: Recommended sampling times^2,3