Part 10 of IVD Hall of Fame
« Prenatal Group B Strep Tests
For most drug therapies, monitoring of drug levels is not necessary. Drug dosages can be adjusted based on clinical response observed in the patient. In a small group of drugs the concentration of the therapeutic is critical, as insufficient levels will lead to under treatment or resistance, while excessive levels will lead to toxicity. By establishing the relationship between drug concentrations and pharmacologic effects, therapeutic drug monitoring (TDM) assays, can be utilized to optimize drug effectiveness without exposing the patient to the additional risks of inappropriate dosage.
TDM refers to the measurement of medication concentrations in blood. It focuses on drugs with a narrow therapeutic range in order to improve patient care by adjusting the dosage of drugs to optimize therapy. Examples of drugs monitored by TDM assays are:
Aminoglycoside antibiotics (gentamicin/tobramicin)
Antiepileptics (carbamazepine/valproic acid)
Immunosuppressants ( cyclosporine/tacrolimus)
Over time the TDM processes have been improved through greater understanding of the pharmacokinetic models for each individual drug and improved forecasting techniques for different populations. Models have been developed that define specific timing for measurement of circulating drug values, to improve the predictive value of monitoring. Active forms of the target drug can often be differentiated from inactive or even toxic breakdown products.
TDM assays do require FDA clearance or approval depending on the specific drug being monitored. Early examples of TDM assays were 510(k) cleared in the late 70’s. Some examples include:
Tobramycin – 1976 – Diagnostic Products ( DPC)
Phenytoin – 1977 – Amersham RIA kit
Carbamazepine – 1978 – Syva EMIT
Immunosuppresants such as Cyclosporin were originally regulated as class III devices. E.I. Dupont Medical Products was successful in downclassifying Cyclosporin through a deNovo application in 2002.
Prior to TDM, dosage of therapeutic drugs was monitored by assessing clinical response to the therapy while observing patients for clinical evidence of toxicity. The capability to precisely monitor therapeutic drug levels and maintain them within the established effective ranges has resulted not only in more successful therapy for patients on these drugs, but has also reduced the incidence of toxicity, tissue damage and long term effects of unnecessary exposure to the drugs.