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
- Monitor patient compliance
- Monitor status during decontamination or detoxification
- Monitor changes in drug concentrations related to aging, pregnancy, or clinical status
TDM should be performed once a drug has reached steady-state concentration.
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, or whole blood specimens are also appropriate for
- Patients on dialysis
- Suspected cases of malabsorption (eg, gastric bypass)
- Evaluating other aspects of an individual patient’s pharmacokinetics
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 to serum/plasma concentrations. The window of drug detection is about 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 drug and metabolite concentrations do not correlate with signs and symptoms of drug therapy or toxicity; therefore, urine should not be a specimen collected 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 the following 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 (0-60 minutes before dose administration)
- Peak (generally 1-2 hours after drug administration; however, this is highly drug dependent)
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