PharmacologyTier 1Medical Sciences concept

Therapeutic drug monitoring - timing and pitfalls

Core concept

TDM is only interpretable if the sample is taken at the correct time relative to dose and relative to steady state -- timing errors are the commonest cause of a misleading level
General rule: check levels at steady state (~4-5 half-lives after starting/changing dose), except when checking for acute toxicity
Trough levels (immediately pre-dose) are the standard for most drugs (gentamicin, vancomycin, phenytoin, lithium, digoxin)

Drug	Correct timing	Common pitfall
Digoxin	>=6-8h post-dose	Earlier sample catches distribution phase -- falsely high
Lithium	12h post-dose (trough)	Any other timing invalidates interpretation
Vancomycin	Trough, pre-dose at steady state	Checking before steady state -> falsely reassuring
Gentamicin	Peak (~1h post) + trough	Used for both efficacy (peak) and toxicity (trough) monitoring
Phenytoin	Trough; consider free level if hypoalbuminaemic	Ignoring albumin -> misinterpreting total level

Trap: a digoxin level drawn shortly after IV/oral dosing (during the distribution phase) will read falsely high and risks inappropriate dose reduction -- always wait the required interval
Levels checked before steady state is reached underestimate the eventual concentration -- do not use an early level to conclude a dose is "subtherapeutic" and escalate prematurely
Toxicity work-up is the exception: check a level immediately regardless of timing when acute toxicity is suspected, and interpret against a nomogram/known kinetics rather than a standard steady-state reference range

Steady-state timing directly follows from half-life (~4-5 half-lives) - drugs with long half-lives (e.g. amiodarone) need levels checked weeks after a dose change
Protein-binding pitfalls (phenytoin, valproate) compound timing errors -- both must be considered together
Same "trough vs peak vs random" distinction applies when interpreting antiepileptic drug levels around missed or extra doses

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