Result Interpretation

Interpreting therapeutic drug monitoring (TDM) results requires a comprehensive approach that considers the patient’s clinical status, dosing history, and potential influencing factors

General Principles of Test Result Interpretation

• Reference Ranges
  • Use appropriate therapeutic ranges for the specific drug and patient population
  • Be aware that therapeutic ranges are guidelines and may need to be individualized
• Clinical Context
  • Interpret test results in the context of the patient’s clinical history, physical examination findings, and other laboratory data
  • Consider the patient’s symptoms, medications, coexisting medical conditions, and response to therapy
• Dosing History
  • Review the patient’s dosing history, including the dose, route of administration, and timing of doses
  • Check for adherence to the prescribed regimen
• Sample Timing
  • Ensure that the specimen was collected at the appropriate time relative to the drug administration schedule (trough, peak, or random)
• Drug Interactions
  • Be aware of potential drug interactions that can affect drug concentrations
  • Check for enzyme inducers, enzyme inhibitors, and other drugs that can alter absorption, distribution, metabolism, or excretion
• Analytical Considerations
  • Understand the limitations of the specific assay used, including its sensitivity, specificity, and potential for cross-reactivity
  • Consider repeating the test using a different method if interference is suspected
• Steady-State Concentrations
  • Ensure that the patient has reached steady-state concentrations before interpreting drug levels
  • Steady state is typically achieved after 5-7 half-lives
• Patient-Specific Factors
  • Consider factors such as age, weight, renal function, liver function, and genetics that can affect drug pharmacokinetics
  • Adjust the therapeutic range based on these factors

Key Concepts in TDM Interpretation

• Therapeutic Range
  • The range of drug concentrations associated with optimal therapeutic effect and minimal toxicity
  • Varies depending on the drug, the indication, and the individual patient
• Trough Level
  • The lowest drug concentration, typically measured immediately before the next dose
  • Used to assess adequate drug exposure and minimize toxicity
• Peak Level
  • The highest drug concentration, typically measured at a specific time after drug administration
  • Used to assess drug efficacy and avoid excessive concentrations
• Area Under the Curve (AUC)
  • A measure of the total drug exposure over a specific time interval
  • Provides a more comprehensive assessment of drug exposure than single-point measurements
• Volume of Distribution (Vd)
  • A measure of the apparent space in the body available to contain the drug
  • Influences the peak concentration after a dose
• Clearance (CL)
  • A measure of the body’s efficiency in eliminating a drug
  • Influences the steady-state concentration
• Half-Life (t1/2)
  • The time it takes for the concentration of a drug in the body to be reduced by one-half
  • Determines the time to reach steady-state and the dosing interval

General Interpretation Guidelines

• Levels Below Therapeutic Range
  • Consider increasing the dose or decreasing the dosing interval
  • Assess patient adherence and drug interactions
  • Consider using a loading dose to achieve therapeutic concentrations more rapidly
• Levels Within Therapeutic Range
  • Continue current therapy and monitor for efficacy and toxicity
  • Assess patient adherence and drug interactions
  • May need to adjust the dose based on clinical response
• Levels Above Therapeutic Range
  • Consider reducing the dose or increasing the dosing interval
  • Assess for drug interactions and renal/hepatic impairment
  • Monitor for signs and symptoms of toxicity
  • In some cases, temporary discontinuation of the drug may be necessary
• Unexpected Results
  • Repeat the test to confirm the result
  • Check for analytical errors or interferences
  • Review the patient’s medical history and medication list
  • Consider alternative analytical methods

Specific Considerations for Different Drug Classes

Aminoglycosides (e.g., Gentamicin)

• Target Concentrations
  • Trough: < 1-2 μg/mL
  • Peak: 5-10 μg/mL (depending on the infection)
• Interpretation
  • Elevated trough levels: Increased risk of nephrotoxicity and ototoxicity
  • Low peak levels: May indicate inadequate dosing or resistance
  • Adjust dosing interval based on trough levels and renal function
• Factors to Consider
  • Renal function: Adjust dose based on creatinine clearance
  • Infection severity: Higher peak levels may be needed for serious infections
  • Concurrent nephrotoxic medications: Avoid use if possible

Cardioactive Drugs (e.g., Digoxin)

• Target Concentrations
  • 0.5-2.0 ng/mL (heart failure)
  • 0.8-1.2 ng/mL (atrial fibrillation)
• Interpretation
  • Elevated levels: Increased risk of cardiac arrhythmias, nausea, vomiting, and visual disturbances
  • Low levels: May indicate inadequate control of heart failure or atrial fibrillation
  • Assess potassium levels: Hypokalemia increases digoxin toxicity
• Factors to Consider
  • Renal function: Adjust dose based on creatinine clearance
  • Electrolyte imbalances: Correct potassium and magnesium deficiencies
  • Drug interactions: Quinidine, amiodarone, and verapamil can increase digoxin levels

Anticonvulsants (e.g., Phenobarbital)

• Target Concentrations
  • 15-40 μg/mL (seizure control)
• Interpretation
  • Elevated levels: Sedation, ataxia, nystagmus, and respiratory depression
  • Low levels: May indicate inadequate seizure control
  • Adjust dosing interval based on half-life and clinical response
• Factors to Consider
  • Protein binding: Monitor free drug levels in patients with altered protein binding (e.g., renal failure, liver disease)
  • Drug interactions: Phenobarbital is a CYP enzyme inducer and can affect the metabolism of other drugs

Antidepressants (e.g., Lithium)

• Target Concentrations
  • 0.6-1.2 mEq/L (acute mania)
  • 0.6-0.8 mEq/L (maintenance)
• Interpretation
  • Elevated levels: Tremor, ataxia, confusion, seizures, and renal toxicity
  • Low levels: May indicate inadequate mood stabilization
  • Monitor for side effects: Polyuria, polydipsia, and thyroid dysfunction
• Factors to Consider
  • Renal function: Adjust dose based on creatinine clearance
  • Sodium balance: Sodium depletion increases lithium levels
  • Drug interactions: Thiazide diuretics, NSAIDs, and ACE inhibitors can increase lithium levels

Immunosuppressants (e.g., Tacrolimus)

• Target Concentrations
  • Vary depending on the type of transplant, the time since transplantation, and the presence of other immunosuppressants
  • Consult the transplant center guidelines for specific target ranges
• Interpretation
  • Elevated levels: Nephrotoxicity, neurotoxicity, hypertension, glucose intolerance, and tremor
  • Low levels: Increased risk of organ rejection
  • Monitor renal function, electrolytes, and glucose levels
• Factors to Consider
  • Hematocrit: Use whole blood specimens and correct for hematocrit
  • CYP3A4 inhibitors and inducers: Numerous drug interactions
  • Gastrointestinal motility: Diarrhea can affect absorption
• Trough level timing and validity
  • Levels taken during the absorptive phase will invalidate results

Key Terms

• Therapeutic Range: Optimal drug concentration range
• Trough Level: Minimum concentration before next dose
• Peak Level: Maximum concentration after dose
• AUC: Total drug exposure over time
• Volume of Distribution: Apparent space for drug distribution
• Clearance: Rate of drug elimination
• Half-Life: Time for concentration to decrease by half
• Steady State: Equilibrium of drug input and output
• Toxicity: Harmful drug effects
• Adherence: Taking medication as prescribed
• Drug Interactions: Effects of other substances on drug levels