Therapeutic drug monitoring

Therapeutic drug monitoring (TDM) is a branch of clinical chemistry and clinical pharmacology that measures  medication levels in blood.

Therapeutic drug monitoring recommended when individualization of drug dose is necessary to promote safety and efficacy of a pharmaceutical agent.

TDMs major focus is on drugs with a narrow therapeutic range.

TDM aims to improve patient care by adjusting the dose of drugs.

TDM can be based on pharmacogenetic, demographic and clinical information, and/or measurement of blood concentrations of drugs or biological or end-point markers of effect.

Variables that influence the interpretation of drug concentration: time, route and dose of drug given, time of blood sampling, handling and storage conditions, precision and accuracy of the analytical method, co-medications, clinical status of the patient, and biologic tolerance to drug therapy.

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

Patients can be identified with different dosage requirements, by utilizing demographic data, clinical findings, clinical chemistry results, and/or, when appropriate, pharmacogenetic characteristics.

A posteriori TDM refers to the readjustment of the dosage of a given treatment in response to the measurement of an appropriate marker of drug exposure or effect. 

TDM includes pre-analytical, analytical and post-analytical phases.

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. 

For certain drugs insufficient levels will lead to undertreatment or resistance, and excessive levels can lead to toxicity and tissue damage.

Indications in favor of therapeutic drug monitoring include established pharmacodynamic relationships between plasma drug concentrations and pharmacological efficacy and/or toxicity.

There is significant patient pharmacokinetic variability, making a standard dosage achieve different concentration levels among patients.

A narrow therapeutic window of the drug, forbids giving high doses in all patients to ensure overall efficacy.

Drug dosage optimization not achievable based on clinical observation alone.

Drug monitoring evaluates the duration of the treatment and criticality for patient’s condition justifying dosage adjustment efforts.

Drug monitoring can relate patient compliance problems.

 TDM determinations can detect and diagnose poisoning with drugs.

Drugs commonly  analyzed for therapeutic drug monitoring:

Aminoglycoside antibiotics (gentamicin)

Antiepileptics (such as carbamazepine, phenytoin and valproic acid)

Mood stabilizers, especially lithium citrate

Antipsychotics (such as pimozide and clozapine)


Ciclosporin, tacrolimus in organ transplant recipients.

Anti-drug antibodies may contribute to low drug concentrations.

Obesity in altered drug metabolism due to genetic differences are among the many factors that may affect drug concentrations and contribute to relative overdosing or under dosing.

Recommended that measurement of itraconazole trough measurements be done in patients requiring long term oral therapy.

TDM increasingly used for therapeutic drugs: antibiotics, small molecule tyrosine kinase inhibitors and other targeted anticancer agents, TNF inhibitors and other biological agents, antifungal agents, antiretroviral agents used in HIV infection, and psychiatric drugs.

Most drugs can be measured in blood or plasma using liquid chromatography, mass spectrometry or gas chromatography, mass spectrometry, which progressively replaced high-performance liquid chromatography. 

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