Therapeutic Drug Monitoring in Special Populations (Tdm Conference)
Clinical Chemistry 1998, Feb, 44, 2
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Publisher Description
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.