Therapeutic Drug Monitoring (TDM): Principles & Target Levels

For most drugs we adjust the dose by clinical response. But for a handful with a narrow therapeutic index, the line between “not working” and “toxic” is razor-thin — so we measure the blood level directly. That is therapeutic drug monitoring (TDM), and it lives entirely inside the band shown below.

When is TDM worthwhile?

Only when the blood level guides therapy better than the clinical effect alone. Classic indications:

• Narrow therapeutic index — small margin between effective and toxic.
• Poor dose–response predictability (e.g. zero-order kinetics — phenytoin).
• A clear concentration–effect relationship, with no easy clinical marker.
• Suspected toxicity, non-adherence, treatment failure, or a major drug interaction.
• Altered pharmacokinetics — renal/hepatic impairment, pregnancy, the extremes of age.

How to sample correctly

• Wait for steady state — about 4–5 half-lives after starting or changing the dose.
• Take a trough level (just before the next dose) for most drugs.
• Special timing: digoxin at least 6 hours post-dose; aminoglycosides often need peak and trough.
• Interpret the level with the patient, never in isolation.

The drugs you must know — and their targets

One trap worth marks: free vs total drug

Most assays report total drug, but only the free fraction is active. In hypoalbuminaemia (or renal failure), total phenytoin looks low while the free, active level is normal — correct for albumin or measure free phenytoin before increasing the dose.

Exam tip: remember the core TDM list — digoxin, lithium, phenytoin, theophylline, aminoglycosides, vancomycin, and the immunosuppressants. Always sample at steady state, usually a trough, and treat the patient, not the number.

TDM is clinical pharmacology in action: it converts a blood level into a safe, effective dose. Master the indications, the timing, and the target ranges, and you can manage every narrow-index drug with confidence.