From the Guidelines
The trough level of a drug should be checked just before the next scheduled dose is administered, when the drug concentration in the body is at its lowest point, specifically within 30 minutes before the fourth or fifth dose to ensure steady state has been reached, as recommended by the Infectious Diseases Society of America 1. This timing is crucial for medications with narrow therapeutic windows such as vancomycin, aminoglycosides (gentamicin, tobramycin, amikacin), anticonvulsants (phenytoin, carbamazepine, valproic acid), immunosuppressants (tacrolimus, cyclosporine), and lithium.
Key Considerations
- For vancomycin, trough serum concentrations should be obtained at steady-state conditions, prior to the fourth or fifth dose, to guide vancomycin dosing 1.
- Monitoring of peak vancomycin concentrations is not recommended, and only trough concentrations are used for monitoring 1.
- The target trough blood level for vancomycin is usually 10 to 15 μg/mL, although a higher blood level, 15 to 20 μg/mL, may be required to treat methicillin/oxacillin/nafcillin-resistant staphylococci with a vancomycin MIC of >1 μg/mL or when there is a lack of microbiological response 1.
- Trough vancomycin monitoring is recommended for serious infections and patients who are morbidly obese, have renal dysfunction (including those receiving dialysis), or have fluctuating volumes of distribution 1.
Clinical Implications
Proper timing of trough level checks is essential because it helps determine if the drug concentration remains above the minimum inhibitory concentration (for antibiotics) or within the therapeutic range (for other medications) throughout the dosing interval, while avoiding toxic accumulation. This ensures both treatment efficacy and patient safety by minimizing the risk of adverse effects from either underdosing or overdosing. Blood samples taken at other times may lead to inaccurate dosing adjustments, highlighting the importance of adhering to the recommended timing for trough level checks.
From the FDA Drug Label
Trough levels provide information about clinically effective serum level range and confirm patient compliance and are obtained just prior to the patient's next scheduled dose. When serum level determinations are necessary, they should be obtained at least 5–7 half-lives after treatment initiation, dosage change, or addition or subtraction of another drug to the regimen so that equilibrium or steady-state will have been achieved
The trough level of a drug should be checked just prior to the patient's next scheduled dose, and at least 5-7 half-lives after treatment initiation, dosage change, or addition or subtraction of another drug to ensure steady-state has been achieved 2.
- Key points:
- Trough levels confirm patient compliance
- Trough levels provide information about clinically effective serum level range
- Steady-state is achieved at least 5-7 half-lives after treatment initiation or changes
- For phenytoin, this is at least 7 to 10 days after initiation of therapy with recommended doses of 300 mg/day
From the Research
Trough Level Checking
The trough level of a drug should be checked at specific times to ensure optimal interpretation of therapeutic drug monitoring (TDM) results.
- The time between when the last dose was taken and the sample was obtained is crucial, with an ideal interval of 10 to 12 hours after the last dose was taken for most orally administered drugs 3.
- For drugs with a half-life of 24 hours, steady state typically occurs when the patient has been taking the same dose for 5 to 7 days 3.
- Trough levels are usually checked before the first morning dose, as this estimate of effect is generally referred to as the 'trough' effect 4.
- In the case of depot medications, trough levels should be obtained at the end of the dosing cycle, just before the administration of the drug, and after the patient has ideally received 4 to 5 injections at equal intervals 3.
Specific Drug Considerations
- For gentamicin, trough levels should be checked to ensure they are within the therapeutic range, with a goal of achieving non-toxic trough concentrations (< 2 mg/l) 5.
- In pediatric patients receiving concurrent vancomycin and aminoglycoside therapy, trough levels of vancomycin and gentamicin should be monitored to minimize the risk of nephrotoxicity 6.
- For drugs with delayed distributional equilibrium and long half-life, trough concentration data can contribute to the evaluation of multiple-dose pharmacokinetics, and early trough samples can be effective for mixed-effects modeling 7.