Therapeutic Drug Assays Should Not Be Performed During the First Two Hours After Oral Administration
Therapeutic drug assays should not be performed during the first two hours after oral administration because during this absorption phase, plasma concentrations are highly variable and do not accurately reflect steady-state drug levels needed for proper therapeutic monitoring. 1
Pharmacokinetic Rationale
During the first two hours after oral administration, most drugs are in the absorption phase, which creates several problems for therapeutic drug monitoring:
- Variable Absorption Rates: During this period, drug absorption is actively occurring and plasma concentrations can fluctuate dramatically 2
- Peak Concentration Variability: The time to reach peak concentration varies between individuals and can be unpredictable during the absorption phase 3
- Non-Representative Levels: Measurements taken during absorption do not represent the average concentration that the patient achieves over the daily dosing interval 2
Proper Timing for Therapeutic Drug Monitoring
For accurate therapeutic drug monitoring, samples should be collected:
- At Steady State: Blood should be collected after the patient has been on a stable dose for at least 5 drug half-lives 1
- During Terminal Elimination Phase: Ideally 12-16 hours after the last dose for most medications taken daily 1
- Before Morning Dose: For most drugs, the appropriate sampling time is immediately before ingestion of the morning dose 1
Why Option A is Correct (Plasma vs. Tissue Concentration)
During the absorption phase (first two hours), plasma concentrations are rising rapidly and do not reflect tissue concentrations. The relationship between plasma and tissue concentrations becomes more stable and predictable only after distribution equilibrium has been reached, which typically occurs after the absorption phase is complete 4.
Why Other Options Are Incorrect
- Option B (all drug in free form): During absorption, drug binding to plasma proteins is occurring, but the issue isn't that all drug is in free form - binding to proteins happens rapidly 4
- Option C (tissue concentration exceeding plasma): While tissue distribution is occurring during absorption, the primary issue is the variability and unpredictability of plasma levels during this phase, not that tissue concentrations exceed plasma concentrations 2
- Option D (drug-metabolite interactions): While metabolism begins shortly after absorption, the primary issue with early sampling is the unpredictable plasma concentrations during absorption, not drug-metabolite interactions 2
Common Pitfalls in Therapeutic Drug Monitoring
- Sampling During Absorption Phase: Taking samples during the first few hours after administration when concentrations are most variable 2
- Ignoring Steady-State Requirements: Failing to wait until the patient has been on a stable dose long enough to reach steady state (typically 5 half-lives) 1
- Inconsistent Timing: Not standardizing the time between last dose and blood sampling 5
By avoiding sampling during the absorption phase (first two hours after administration), clinicians can obtain more reliable and interpretable drug concentrations that better reflect the patient's average exposure to the medication, leading to more appropriate dosing decisions and improved clinical outcomes.