When should a plasma sample be obtained to reflect a trough drug level in a patient in steady state?

Timing of Trough Drug Level Sampling at Steady State

For a patient at steady state, plasma samples to reflect trough drug levels should be obtained immediately before the next scheduled dose—typically 12-16 hours after the last dose for twice-daily regimens, or approximately 24 hours after the last dose for once-daily regimens. 1

Understanding Steady State Requirements

Before obtaining a trough level, the patient must have reached steady-state conditions, which occurs after approximately 5 drug half-lives following initiation of therapy or any dose change 1, 2, 3. For most drugs, this translates to:

• 1 week (5-7 days) after stable daily dosing for drugs with typical half-lives 1
• 24-48 hours for beta-lactam antibiotics when a loading dose is used 1
• Before 24 hours for beta-lactam antibiotics with loading doses 1

Specific Timing Recommendations by Administration Schedule

For Intermittent Dosing (Most Oral Medications)

Draw blood immediately before ingestion of the morning dose, which represents:

• 12-16 hours after the last medication for twice-daily dosing 1, 2
• 24 hours after the last dose for once-daily regimens 1, 2

This timing ensures the sample reflects the terminal β-elimination phase and avoids interference from the absorption phase 1.

For Continuous Infusions

Measure plasma steady-state concentrations rather than trough levels, as the drug is continuously administered 1.

For Specific Drug Classes

Vancomycin (IV):

• Obtain trough levels just before the fourth dose at steady state 1
• This typically occurs immediately before the next infusion 1

Depot Medications (e.g., long-acting antipsychotics):

• Sample at the end of the dosing cycle, just before the next injection 3
• After the patient has received 4-5 injections at equal intervals to approach steady state 3

Beta-lactam antibiotics:

• For intermittent dosing: measure plasma trough concentration 1
• Perform TDM 24-48 hours after treatment onset or any dosage change 1

Critical Variables That Must Be Documented

When obtaining and interpreting trough levels, you must record three essential variables 3:

1. The prescribed dose the patient is taking
2. Confirmation of steady-state achievement (≥5 half-lives at stable dosing)
3. Exact time interval between last dose and sample collection

Without this information, the trough level cannot be properly interpreted 3.

Common Pitfalls to Avoid

Timing errors that invalidate results:

• Sampling too soon after dose changes before steady state is reached produces misleading results 2, 3
• Drawing during the absorption phase (within 3-10 hours of oral dosing) yields falsely elevated and unpredictable concentrations 1
• Random timing rather than true pre-dose sampling fails to reflect the trough concentration 2

For once-daily evening dosing:

• A morning blood draw (12-15 hours post-dose) will be 18-25% higher than the true trough 4
• Waiting 18-21 hours post-dose yields values only 3-13% higher than trough, which may be acceptable 4

When to Repeat Trough Levels

After achieving steady state and documenting an appropriate trough level, routine repeat monitoring is generally not necessary unless 1, 3:

• Significant clinical changes occur (circulatory, renal, or hepatic function changes) 1
• New drug interactions are introduced that may alter metabolism 1
• Therapeutic interventions are implemented (fluid expansion, albumin, catecholamines, renal replacement therapy) 1
• Clinical deterioration or suspected toxicity develops 2

The trough level reflects the patient's drug clearance capacity, which remains stable unless these factors change 3.