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Key reviewer: Associate Professor Chris Florkowski, Chemical Pathologist, Canterbury Health Laboratories,
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:
- There is an established relationship between blood drug concentration and therapeutic response and/or toxicity
- There is a poor relationship between blood drug concentration and drug dosage
- There are clear clinical indications for the test (such as: no response to treatment; suspected non-compliance; signs
- The specimen can be provided, appropriately timed and dated, with identifiable patient information
- 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
Details to include on the request form
Table 1: Information required on request form1
|Time sample collected
|Time dose given
|Dosage regimen (dose, duration, dosage form)
|Patient demographics (age/sex)
|Other relevant co-morbidities (e.g. renal/liver disease)
|Indications for testing (e.g. ? toxicity, non-compliance)
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 times2,3
||Time to steady state
||Recommended sampling time
||Immediately pre dose
||Reduced clearance can occur in children, after chronic therapy and with other anti-convulsants.
||6–24 hours post dose
||In renal failure, may take up to 3 weeks to reach steady state.
Routine monitoring not recommended.
||12 hours post dose or Immediately pre dose
||Reduced clearance in children.
Decreased renal function may lead to increased concentration, especially in the elderly. Drug accumulation
is enhanced by dehydration.
||Immediately pre dose
||Time to steady state may depend on dose. Altered clearance when taken with other anticonvulsants.
||2–4 hours post dose
||Prolonged clearance in neonates, reduced clearance in children. Prolonged clearance in severe illness
notably respiratory failure and CHF.
||Immediately pre dose
||Reduced clearance when taken with enzyme inducers e.g. phenobarbitone, phenytoin. There is poor
correlation between valproate levels and clinical effect. The main reason for measurement is to assess compliance.
- Gross AS. Best practice in therapeutic drug monitoring. Br J Clin Pharmacol 1998;46:95-99
- Medicines information centre, Calderdale Royal Hospital. Available from:
- Kyle C (Ed), A Handbook for the Interpretation of Laboratory tests. 4th Edition, 2008, Diagnostic Medlab.