Therapeutic Drug Monitoring and Optimal Pharmacotherapy with Medicines of Narrow Therapeutic Index

Abstract

Therapeutic drug monitoring (TDM) remains an under-utilized approach in giving life to the practice of personalized medicine, as it is the medical practice of measuring certain medications at intervals to ensure a constant plasma drug concentration and to optimize dosage regimens. It can be used to enhance patient treatment outcomes due to clear dose-response relationships. TDM also reduces the overall cost of healthcare. Unfortunately, most drugs cannot be monitored with TDM due to the cost and turnaround times, but rather those with a narrow therapeutic indices (e.g. digoxin, lithium, phenytoin, vancomycin, etc.) which have a high risk of causing adverse effects. Also, drugs with significant pharmacokinetic variability as well as those with difficult-to-monitor clinical endpoints are TDM candidates. TDM and its associated benefits in optimizing therapy can only be attained if the method is adequately unified with treatment. TDM processes assume that there is a significant relationship between dose and plasma drug concentration and between the latter and pharmacodynamic properties of the drug. TDM takes into consideration the patient indication and other factors such as weight, age, concomitant drug therapy, and organ function in defining an appropriate initial dosage regimen. Also, patient compliance to treatment, pregnancy, and drug interactions are to be considered as they are major sources of pharmacokinetic variability and may have to be considered when interpreting TDM results. In the interpretation of TDM measurements, sampling time with drug dose, dosage history, patient response, and the desired medicinal targets need to be established. Genetic polymorphisms, smoking, drug formulation, and methodology used in testing may also affect the results. TDM also aims to optimize clinical outcomes in patients with various clinical scenarios in terms of appropriate concentrations of difficult-to-manage medications. TDM is thus a multidisciplinary discipline involving scientists, pharmacists, clinicians, and nurses, and collaboration is recommended to ensure that best practice is attained to patients’ benefit.