Therapeutic Drug Monitoring

This section provides a comprehensive overview of TDM

Pharmacokinetics (PK)

Definition: The study of how the body affects a drug after administration (ADME)
ADME Processes
- Absorption: Entry of drug into the bloodstream
- Distribution: Transport of drug to tissues
- Metabolism: Chemical alteration of drug
- Excretion: Elimination of drug and metabolites
Key PK Parameters
- Bioavailability: Fraction of drug reaching systemic circulation
- Volume of Distribution (Vd): Apparent space in the body available to contain the drug
- Clearance (CL): Rate of drug removal from the body
- Half-Life (t1/2): Time for drug concentration to decrease by half
Therapeutic Range
- The range of drug concentrations associated with optimal therapeutic effect and minimal toxicity
Therapeutic States
- Subtherapeutic: Below therapeutic range
- Therapeutic: Within therapeutic range
- Toxic: Above therapeutic range
- Supratherapeutic: Above therapeutic range

Importance: Properties influence ADME, mechanism of action, and analytical methods
Key Properties
- Solubility: Affects absorption and excretion
- Ionization: Influences absorption, distribution, and renal excretion
- Protein Binding: Affects distribution and free drug concentration
- Partition Coefficient (Log P): Affects membrane permeability
Drug Classes and Properties
- Aminoglycosides: Water-soluble, polycationic
- Cardioactive Drugs: Variable properties
- Anticonvulsants: Lipid-soluble
- Antidepressants: Variable properties
- Immunosuppressants: Lipid-soluble, highly protein-bound

Analytical Principles
- Immunoassays: Antibody-antigen binding
- Chromatography: Separates compounds
- Mass Spectrometry: Measures mass-to-charge ratio
Specimen Collection and Handling
- Timing of Dose: Trough, peak
- Collection Tubes: Correct type to minimize interference
- Processing: Centrifugation, separation, storage
Quality Control
- Use QC samples to validate accuracy
- Calibrate instruments routinely

Reference Intervals
- Use appropriate reference ranges
Clinical Context
- Patient history, symptoms, medication list
Influence of Other Variables
- Drug-drug interactions
- Age, Weight, etc
Common Findings
- Drug level results below, above, or within the therapeutic range
Limitations
- Consider test specificity

Renal Disease: Affects excretion
Liver Disease: Affects metabolism
Heart Failure: Affects distribution
Gastrointestinal Disorders: Affects absorption
Obesity: Alters distribution
Pregnancy: Alters all ADME phases
Other Correlations
- Other diseases or conditions that may alter the distribution, metabolization, and excretion