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Therapeutic Drug Monitoring - TDM. ARUP Consult®. Retrieved December 30, 2024, https://arupconsult.com/content/therapeutic-drug-monitoring

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Therapeutic Drug Monitoring - TDM

Last Literature Review: May 2022 Last Update:

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Medical Experts

Contributor
Contributor

McMillin

Gwendolyn A. McMillin, PhD
Gwendolyn A. McMillin, PhD
Professor of Pathology (Clinical), University of Utah
Scientific Director, Mass Spectrometry Platform; Medical Director, Clinical Toxicology and Pharmacogenomics, ARUP Laboratories

Therapeutic drug monitoring (TDM) refers to the clinical practice of measuring drugs and/or metabolites in blood or serum/plasma at a specific time point to determine if a patient’s drug concentrations are within the therapeutic range and confirm concentrations are neither subtherapeutic nor potentially toxic. The purpose of TDM is to optimize dosing to target a therapeutic plasma drug concentration while minimizing toxicity. TDM is often influenced by pharmacogenetics (PGx) factors. Refer to the ARUP Consult Germline Pharmacogenetics - PGx topic for detailed information about PGx testing and recommendations.

Quick Answers for Clinicians

What is the purpose of therapeutic drug monitoring?

Effective drug treatment is dependent on patient adherence/compliance to prescribed medications. Drug treatment and dosage should be personalized for each patient due to interindividual variability in response to therapy. Therapeutic drug monitoring (TDM) allows for personalization of drug selection and dose, evaluation of adherence, and investigation of changes in pharmacokinetics (eg, drug-drug interactions). In many cases, germline pharmacogenetics (PGx) testing can inform TDM testing.

When should therapeutic drug monitoring be performed?

Therapeutic drug monitoring (TDM) should be performed when the patient has achieved steady-state concentration, has changed drug therapy, or has had a change in response to treatment (eg, toxicity).

Which specimens are appropriate for therapeutic drug monitoring?

Whole blood, serum, and plasma specimens can be used to assess whether the drug dosage achieved the targeted therapeutic range and to evaluate patient adherence. Urine drug and metabolite concentrations do not correlate with signs and symptoms of drug therapy or toxicity and should not be used for therapeutic drug monitoring (TDM).

How should therapeutic drug monitoring results be interpreted?

Test results should be interpreted relative to the established therapeutic range, dose-related range, or toxic range (if applicable); timing of specimen collection (eg, predose [trough], peak, or random); specimen type; and the patient’s clinical response to treatment. Results can be affected by several variables. Incorrect timing of specimen collection relative to the therapeutic range can be misleading. Response to drug therapy is also influenced by the patient’s pharmacogenetics (PGx), ie, whether they demonstrate normal, rapid, or poor drug metabolism; physical conditions (eg, pregnancy, comorbidities); and drug-drug or food-drug interactions that could lead to an increase, decrease, or inhibited response to therapy.

Indications for Testing

Not all medications require TDM, especially when the drug has a wide therapeutic index or low risk for severe adverse effects. TDM is utilized for drugs with a:

  • Known relationship between dose and blood/serum/plasma concentrations
  • Narrow therapeutic window
  • High patient variability in pharmacokinetics (eg, drug liberation, absorption, distribution, metabolism, and elimination)
  • Potential for severe adverse effects (dose related)

TDM is also used to identify drug-drug or food-drug interactions and to monitor patient compliance with treatment, status during decontamination or detoxification, and changes in drug concentrations related to aging, pregnancy, or clinical status. A list of example drug-drug interactions that may be identified by TDM can be found on the U.S. Food and Drug Administration’s Drug Development and Drug Interactions web page. 

TDM should be performed once a drug has reached steady-state concentration.

Specimen Selection

Therapeutic and toxic ranges are typically established for serum, plasma, and whole blood specimens. Urine should not be utilized for TDM.

Serum/Plasma and Whole Blood

Clinical signs and symptoms of effective drug treatment, ineffective drug treatment, and toxicity may correlate with drug and/or metabolite concentrations in serum, plasma, and/or whole blood.

Serum, plasma, and whole blood specimens are also appropriate for patients on dialysis, for suspected cases of malabsorption (eg, due to gastric bypass), and for evaluating other aspects of an individual patient’s pharmacokinetics.

Whole Blood

Whole blood specimens are used for TDM of select drugs such as immunosuppressive drugs (eg, cyclosporine A, tacrolimus, everolimus, sirolimus, and thiopurine drugs) due to drug accumulation in red blood cells (RBCs).

Oral Fluid (Saliva)

Oral fluid drug concentrations tend to correlate with serum/plasma concentrations. The window of drug detection is approximately 1-2 days after drug use; therefore, oral fluid can be used to detect recent drug exposure. Therapeutic ranges are not well established in oral fluid.

Urine

Urine drug and metabolite concentrations do not correlate with signs and symptoms of drug therapy or toxicity; therefore, urine is not a recommended specimen type for TDM. Urine drug concentrations should also not be used to extrapolate the dose that was administered.

Timing of Specimen Collection

Therapeutic ranges are typically established at timed blood collections after steady-state concentrations have been reached (generally 5-7 half-lives after initiation of or change in dosing):

  • Trough or predose concentrations (0-60 minutes before dose administration)
  • Peak concentrations (generally 1-2 hours after drug administration; however, this is highly drug dependent)
  • Random concentrations

Commonly Used Testing Strategy

Quantitative testing for TDM may be performed by immunoassay, high performance liquid chromatography (HPLC), or mass spectrometry. Drug results that are reported as less than the assay cutoff should be interpreted as “not detected.”

Frequently Asked Questions

What is the definition of half-life?

The half-life of a drug refers to the time it takes for 50% of the drug to be eliminated from blood.

What is the definition of steady-state concentration?

Steady-state concentration occurs when the rate of drug administration is equal to the rate of elimination. Generally, steady-state concentration can be achieved after an individual has consistently received the drug for the duration of 5-7 half-lives (eg, if a drug has a half-life of 24 hours and is administered once a day, then steady-state concentration can be achieved after 5-7 days of drug administration).

What is the window of detection of drugs in blood, serum, or plasma specimens?

In general, the window of detection in blood, serum, and plasma is 1-2 days after drug administration.

The window of detection for drugs is dependent on several factors, including the following:

  • Half-life of the drug
  • Drug dose
  • Frequency of drug administration
  • Route of administration
  • Drug formulation
  • Chemistry of the drug (eg, solubility, stability)
  • Patient age
  • Patient body composition and sex
  • Patient pathophysiology and pharmacokinetics
  • Coadministration of other medications
  • Hydration and nutrition status
  • Analytic limitations of testing

Can gel separator tubes be used for toxicology testing?

Gel separator tubes are not recommended for testing in toxicology. Drugs that are lipid soluble may be absorbed into the gel and may cause a falsely low drug result.

ARUP Laboratory Tests

Refer to the Germline Pharmacogenetics topic for detailed information about PGx testing and recommendations related to the drug targets listed below.

Antiarrhythmic Tests

Antibiotic Tests

Antibody Therapeutic Tests

Anticoagulant Tests

Anticonvulsant/Antiepileptic Tests

The therapeutic range is based on serum predose (trough) draw at steady-state concentration.

Antidepressant Tests

Antidiabetic Tests

Antifungal Tests

Antihypertensive Tests

Antipsychotic Tests

Immunosuppressant Tests

Miscellaneous Tests

Nonopioid Pain Medication Tests

Also refer to ARUP Consult’s Drug Testing topic.

Oncology/Chemotherapy Tests

Opiate/Opioid Analgesic Tests

Note: Also refer to ARUP Consult’s Drug Testing topic.

Sedative-Hypnotics Tests

(eg, for benzodiazepines, barbiturates, muscle relaxants)

 

References