M06.01.12 Therapeutic Drug Monitoring

Overview: Therapeutic drug monitoring (TDM) is a clinical practice that involves measuring drug concentrations in patients’ blood or other biological fluids to optimize drug therapy. TDM aims to ensure that drug concentrations remain within a therapeutic range, balancing efficacy and safety.

Key Concepts:

1. Rationale for TDM:
   • Some drugs have a narrow therapeutic index, meaning that small changes in drug concentrations can lead to significant changes in therapeutic or toxic effects.
   • Individual variability in drug pharmacokinetics (e.g., absorption, metabolism, excretion) can lead to differences in drug concentrations among patients receiving the same dose.
   • TDM can help personalize drug therapy by adjusting dosages based on individual patient characteristics, such as age, weight, renal function, and genetics.
2. Indications for TDM:
   • Drugs with a narrow therapeutic index, such as certain antiepileptic drugs, immunosuppressants, antibiotics, and anticoagulants.
   • Drugs with wide interpatient variability in pharmacokinetics or pharmacodynamics, such as some psychotropic medications.
   • Patients with factors that may affect drug metabolism or clearance, such as hepatic or renal impairment, drug interactions, or extremes of age.
3. TDM Process:
   • Sample Collection: Blood, plasma, serum, or other biological fluids are collected at specified times after drug administration.
   • Analytical Assay: Drug concentrations are measured using analytical techniques such as immunoassays, chromatography, or mass spectrometry.
   • Interpretation: Drug concentrations are compared to established therapeutic ranges, which may vary based on the drug, indication, and patient characteristics.
   • Clinical Decision-Making: Clinicians use TDM results to adjust drug dosages, optimize therapy, and minimize the risk of adverse effects or treatment failure.
4. Clinical Applications of TDM:
   • Dose Optimization: TDM helps ensure that patients receive adequate drug concentrations to achieve therapeutic efficacy while minimizing the risk of toxicity.
   • Individualized Therapy: TDM allows for personalized dosing regimens tailored to individual patient factors, optimizing treatment outcomes.
   • Monitoring Compliance: TDM can detect non-adherence to medication regimens by assessing drug concentrations in biological fluids.
5. Challenges and Limitations:
   • Availability of Assays: Not all drugs have readily available assays for TDM, limiting its applicability to certain medications.
   • Interpretation of Results: Interpretation of TDM results requires consideration of various factors, including drug kinetics, patient characteristics, and clinical context.
   • Cost and Resources: TDM may be costly and resource-intensive, requiring specialized equipment, trained personnel, and timely turnaround of results.

Bibliography:

1. Dasgupta A, Wahed A. Therapeutic Drug Monitoring: Techniques and Interpretation. New York: Humana Press; 2002. DOI: 10.1385/1-59259-243-4.
2. Roberts MS, Stokes JA, King MA, et al. Therapeutic drug monitoring of antimicrobials. Br J Clin Pharmacol. 2012; 73(1): 27-36. DOI: 10.1111/j.1365-2125.2011.04025.x.
3. van der Weide J, Steijns LS, van Weelden MJ, et al. The effect of genetic polymorphism of cytochrome P450 CYP2D6 on haloperidol pharmacokinetics and on the outcome of haloperidol treatment. Clin Pharmacol Ther. 2003; 74(6): 483-494. DOI: 10.1016/j.clpt.2003.08.008.

These references provide comprehensive information on therapeutic drug monitoring, including its rationale, indications, process, clinical applications, and challenges.