Therapeutic Drug Monitoring (TDM)
Therapeutic drug monitoring (TDM) is commonly used to help physicians monitor and maintain drug levels within the therapeutic window. The therapeutic window is the concentration range in which a drug exerts its clinical effect with minimal adverse effects for most patients. TDM is particularly useful for monitoring drugs that are used long-term or drugs that have a narrow therapeutic range. Special circumstances may require both peak and trough measures to monitor achievement of short-term therapeutic concentration (peak) and clearance of drug to avoid toxicity (trough). TDM is also useful to detect and monitor drug interactions and identify inadequate adherence as a cause of poor treatment response. It is important to recognize that the pharmacokinetics of each drug may vary with patient age, sex, weight, clinical status, and the presence of other drugs. TDM parameters are generalized guidelines and are not meant to replace patient assessment and clinical judgment.
Once steady state has been reached, peak and/or trough serum samples may be collected after the next scheduled dose. For peak samples, that would typically be 2 to 3 hours after an oral dose, 30 to 60 minutes after an intravenous dose, 2 to 4 hours after an intramuscular dose, or 1 to 1.5 hours after an intranasal dose. Trough samples are drawn just before administration of the next scheduled dose. TDM of aminogly coside antibiotics, such as gentamicin and amikacin, requires determination of both peak and trough concentrations for multiple daily dosing regimens. Only trough concentrations are measured for most other drugs.
1. Request for drug level
Drug concentration measurements are generally requested for the following reasons:
• Monitoring the patient’s therapy
• Patient lacks proper response
• Help detect potential hazard(s) due to other medications
• Confirm suspects toxicity
• Monitor for patient’s compliance with therapy
2. The biological sample
Blood samples are usually collected at steady state to obtain clinically useful serum drug concentrations. When a fixed dose is administered at regular intervals, a drug will accumulate in the body during the absorption phase until it reaches steady state, during which the rate of drug intake equals the rate of drug elimination. The time required to reach steady state depends on the elimination half-life of the drug, defined as the time required for the serum drug concentration to decrease by 50%. The half-life is itself determined by the metabolism and excretion rates of the drug. Under conditions of first-order kinetics in a one-compartment distribution model (drug is rapidly and evenly distributed throughout the body) and in the absence of a loading dose, at least 5 half-lives are required to achieve a steady state.
Some drugs are metabolized by non–first-order kinetics and undergo extensive first-pass metabolism in the liver and/or follow multi-compartment distribution in the body (drug is distributed into plasma at one rate then exchanged between plasma and tissues at a different rate). The time required for these drugs to reach a steady state may differ from the conventional 5 half-lives. (The time to completely eliminate a discontinued drug that had reached steady state, may be equivalent to the time that was required to reach steady state.) Except in medical emergencies, the monitored drug should be allowed to reach a new steady state following a dosage change and the addition or discontinuation of a co-administered drug.
For most TDM drugs, analysis is performed on serum venipuncture specimen collections using plain red-top tubes. Serum should be clear and free of red cells. Please check individual specimen requirements for restrictions or alternate specimens. Serum Separator Tubes (SST®) should not be used to collect specimens for TDM. The polyester separator gel may extract or otherwise impact lipophilic substances (most drugs), and can cause a falsely low drug concentration result.
3. The Request
The following information is needed in order to properly interpret the drug concentration:
• Time the blood sample was taken
• Time dosage was received
• Dose, duration, dosage form
• Patient demographics
• Indication for monitoring
• Pharmacokinetics and therapeutic range of the drug
4. Laboratory Measurement
Quality results begin with the way in which a specimen is collected and prepared for analysis. Our Directory of Services provides expanded instructions on Specimen Collection and Handling prior to the alphabetical listing of our most commonly ordered tests. For easy usability, we have lightened the weight of the Directory from prior years by placing information about Clinical Significance and the ever-growing Test Selection/Interpretation tab on our website QuestDiagnostics.com.
As part of an extensive set of activities focused on quality, we have a formal Quality Assurance Program that monitors and evaluates the quality of the testing process (preanalytic, analytic and postanalytic). This Quality Assurance Program has both local and national components.
Each laboratory site carries out an extensive Quality Assurance plan that provides for systematic monitoring of the quality and appropriateness of services. The National Quality Assurance department monitors general laboratory performance across the Quest Diagnostics network and supports the local Quality Assurance activities through laboratory inspections, tracking of proficiency testing outcomes, and other programs.
Our goal is to become the first laboratory in our industry to aspire to virtually error-free performance by embracing the principles of Six Sigma Quality, measurable set of interrelated business objectives, based on the Voice of the Customer.
5. Laboratory Communication of Results
Routine test result reporting times vary, depending upon the nature of the test, the analytical time required for the procedure and the method of reporting. Reports are delivered electronically, by facsimile, U.S. Mail, or by the Quest Diagnostics logistics team.
TDM laboratory test reports contain many key pieces of information:
• Test name
• Identification of measurands (analytes) included in the testing
• Analytical results including high or low flagging as appropriate
• Units of measure
• Reference or therapeutic range
• Disclosure of the laboratory performing site
• Some reports may contain additional information for results interpretation
6. Clinical Interpretation
We want to make it easy for you to get the diagnostic services and health information you need from Quest Diagnostics. We have a dedicated service team to support your needs. Our network of more than 800 M.D.’s, Ph.D.’s, and academic associates are available for consultation. We offer broad access to laboratory services through our nationwide network of Regional Laboratories, Rapid Response Laboratories and conveniently located Patient Service Centers.
7. Therapeutic Management
Change in drug dosage is a function of patient assessment and clinical judgment. TDM provides objective laboratory data that is incorporated into the decision but is not the sole basis for change in treatment strategy.
For more information on further tests check the available tests section.