Therapeutic drug monitoring

Therapeutic drug monitoring (TDM) is a branch of clinical chemistry and clinical pharmacology that specializes in the measurement of medication concentrations in blood. Its main focus is on drugs with a narrow therapeutic window. TDM aims at improving patient care by adjusting the dose of drugs for which clinical experience or clinical trials have shown it improved outcome in the general or special populations. It can be based on a priori pharmacogenetic, demographic and clinical information, and/or on the a posteriori measurement of blood concentrations of drugs (pk/pd monitoring).

There are numerous variables that influence the interpretation of drug concentration data: time, route and dose of drug given, time of blood sampling, handling and storage conditions, precision and accuracy of the analytical method, validity of pharmacokinetic models and assumptions, co-medications and clinical status of the patient.

Many different professionals (physicians, clinical pharmacologists, clinical pharmacists, nurses, medical laboratory scientists, etc.) are involved with the various elements of drug concentration monitoring, which is a truly multidisciplinary process, because failure to properly carry out any one of the components can severely affect the usefulness of using drug concentrations to optimize therapy. An organized approach to the overall process is critical.

A priori
A priori TDM consists of determining the initial dose regimen to be given to a patient, based on clinical endpoint and established on population (PK/PD) relationships. These relationships help to identify sub-populations of patients with different dosage requirements, by utilizing demographic data, clinical findings, and clinical chemistry results.

A posteriori
A posteriori TDM includes pre-analytical, analytical and post-analytical phases, each with the same importance. It is most often based on the specific, accurate, precise and timely determinations of the active and/or toxic forms of drugs in biological samples collected at the appropriate times in the correct containers (PK monitoring).

Characteristics of drugs subject to TDM
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. In a small group of drugs, this is impossible, as insufficient levels will lead to undertreatment or resistance, and excessive levels can lead to toxicity and tissue damage.

Indications for therapeutic drug monitoring include:
 * There is an experimentally determined relationship between plasma drug concentration and the pharmacological effect.
 * Knowledge of the drug level influences management.
 * There is a narrow therapeutic window.
 * There are potential patient compliance problems.
 * The drug dose cannot be optimised by clinical observation alone.

Examples of drugs analysed by therapeutic drug monitoring:
 * Aminoglycoside antibiotics (gentamicin)
 * Antiepileptics (such as carbamazepine, phenytoin and valproic acid)
 * Mood stabilisers, especially lithium citrate
 * Antipsychotics (such as pimozide and clozapine)
 * Biologic monoclonal antibody drugs (such as adalimumab, certolizumab pegol and infliximab)

Therapeutic drug monitoring can also detect poisoning with above drugs, should the suspicion arise.