Therapeutic Drug Monitoring in Special Populations (Tdm Conference‪)‬

Therapeutic drug monitoring (TDM) is the process of quantifying drug concentrations in patients and using these measurements to design individualized dosing regimens (dose, formulation, route, and frequency of administration) [1]. TDM is relatively new, but the potential for TDM to improve care is being increasingly recognized [2-7]. When performed correctly, TDM has been shown to efficiently maximize efficacy and minimize toxicity in many patient populations [8,9]. TDM has become a routine method to maintain "therapeutic" concentrations of numerous drugs [10]. However, it requires drug concentrations to be interpreted for each specific patient's complete clinical, pharmacokinetic, and pharmacodynamic information. Unfortunately, too many laboratories report (and laboratory certifying bodies accept) "numbers only"--i.e., concentration without complete and accurate medical and drug dosing information. When done poorly, as in a "numbers only" laboratory, TDM has not been effective [11] and can be dangerous [12]. For decades, clinicians have recognized that different patients given the same dose of a medication, even in an identical formulation, might have qualitatively or quantitatively different responses [1]. Not until reliable measurements of drug concentrations in bodily fluids became available, however, was it proven that many of these differences in dose/response relationships were the result of large interindividual differences in drug concentrations achieved in patients given identical doses. These dose/ concentration differences were shown to be the result of wide interindividual variations in the absorption, distribution, and elimination of medications: pharmacokinetics (PK) (1). These PK differences explained most of the interindividual differences in dose/response relationships. More recently, some differences in concentration/response relationships (pharmacodynamics; PD) have also been verified. Interindividual variations in PK and PD are especially important in "special populations," who are more likely to either under- or overrespond to usual dosing regimens; who are least able to tolerate, recognize, or communicate drug effects; who have organ dysfunction; or who are intentionally or accidentally dosed incorrectly. I will here review some examples of special populations where TDM is useful to either predict or prevent toxicity or improve therapeutic outcomes. This review will not be exhaustive; rather I will concentrate on some of the more common or clinically most meaningful situations.