Therapeutic Drug Monitoring

Therapeutic Drug Monitoring

1. Definition, scope, and historical context

• Therapeutic drug monitoring (TDM) is the use of validated assay procedures to determine drug concentrations in a biological matrix (most commonly plasma or serum), with interpretation and individualisation of dosage regimens so that the resulting concentration falls within a population-derived therapeutic range associated with efficacy and acceptable toxicity (Spruill 7e Les.1, pp.4–6).
  • Distinguished from pharmacokinetics (study of ADME — time course of drug movement) and clinical pharmacokinetics (bedside application of PK to safe/effective therapeutics) (Spruill 7e Les.1, pp.1–2).
  • Distinguished from pharmacodynamics (concentration-effect relationship at the receptor site); TDM is meaningful only when PD is predictably linked to plasma concentration through kinetic homogeneity (Spruill 7e Les.1, pp.1–3).
• The operational definition in MD-level practice combines four steps: (i) drug selection, (ii) dosage-regimen design, (iii) measurement of a plasma concentration, and (iv) feedback adjustment of the regimen using patient-specific PK parameters (Shargel 8e Ch.23, pp.1–4).
• Conceptual goal: maximise probability of therapeutic benefit while minimising probability of toxicity in a patient whose individual PK deviates from the population average (KDT 8e Ch.3, pp.42–43).
  • Secondary uses recognised in the modern definition: assessment of medication adherence, indirect surrogate of organ function, screening for drug abuse, and toxicology/overdose evaluation (Shargel 8e Ch.23, pp.5–7).
• TDM evolved alongside three converging developments (Shargel 8e Ch.23, pp.1–4; Spruill 7e Les.1, p.4):
  • Recognition of interpatient PK variability (3-fold or greater between patients on the same mg/kg dose).
  • Availability of sensitive immunoassays (fluorescence polarisation, EMIT, CLIA) able to detect ng/mL–µg/mL concentrations in <1 mL of serum.
  • Pharmacokinetic modelling that linked dosing rate to steady-state concentration via clearance (C̄pss = dose-rate / CL).
• Modern terminology overlap: TDM, Clinical Pharmacokinetic Service (CPKS), and Medication Therapy Management (MTM) are not synonymous but their workflows overlap; in the US the CMS programme for MTM was created in the Medicare Modernization Act 2003 and includes annual medication review, follow-up, counselling, and identification of medication-related problems (Shargel 8e Ch.23, p.2).