Therapeutic drug monitoring

A priori TDM consists of determining the initial dose regimen to be given to a patient, based on clinical endpoint and on established population pharmacokinetic-pharmacodynamic (PK/PD) relationships.

TDM encompasses all aspects of this feedback control, namely:[2] In pharmacotherapy, many medications are used without monitoring of blood levels, as their dosage can generally be varied according to the clinical response that a patient gets to that substance.

Yet, TDM is not limited to the provision of precise and accurate concentration measurement results, it also involves appropriate medical interpretation, based on robust scientific knowledge.

The interpretation of a drug concentration result goes through the following stages:[8] Ideally, the usefulness of a TDM strategy should be confirmed through an evidence-based approach involving the performance of well-designed controlled clinical trials.

Model-informed precision dosing (MIPD) should enable significant progress to be made in taking into account the many factors influencing drug response, in order to optimize therapies (a priori TDM).

TDM interpretation: an anticancer drug is given to a patient at a dosage of 400 mg every day at 8:00 am. A TDM sample is obtained at 6:00 am, showing a drug concentration of 0.46 mg/L. 1) Regarding “normality”, the result is around the 25th percentile, suggesting a rather high drug clearance in this patient. 2) Regarding “appropriateness”, the result suggests that the patient's most likely concentration curve (green dashed line) passes below the acceptance range of 0.75 to 1.5 mg/L at trough, raising concerns about treatment efficacy. 3) Regarding dosage adjustment to recommend, this TDM result suggests that a doubled dose of 800 mg daily might be suitable to drive the concentration curve close to target (blue dotted line). Note that this interpretation assumes that the patient's adherence to prescription is good, and that the sample measurement is accurate.