Therapeutic Drug Monitoring

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 are neither subtherapeutic nor potentially toxic. The purpose of TDM is to optimize dosing to target a therapeutic plasma drug concentration while minimizing toxicity.

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. TDM allows for personalization of drug selection and dose, evaluation of adherence, and investigation of changes in pharmacokinetics (eg, drug-drug interactions).

Therapeutic drug monitoring should be performed once the patient has achieved steady-state concentration, and when there are changes to drug therapy and/or changes in response (eg, toxicity).

Whole blood, serum, and plasma specimens can be used to assess if drug dosage avhieved the targeted therapeutic range and patient adherence. Urine specimens can be used to assess patient adherence to medication by detecting parent drug and metabolites.

Specimen Selection

Therapeutic and toxic ranges are typically established in the following specimen types: serum, plasma, and whole blood.

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

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 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

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.