20 Therapeutic drug monitoring (TDM)

Abstract

The measurement of plasma concentrations of drugs given in therapy (therapeutic drug monitoring, TDM) is useful for a small number of compounds for which pharmacological effects cannot be easily assessed and for which the margin between adequate dosage and potentially toxic dosage is small. Thus, for some anticonvulsants, notably phenytoin, anti-infective agents (antimalarial, antimicrobial, and antiretroviral drugs), cardioactive drugs including digoxin, most immunosuppressants, and certain psychoactive drugs (notably clozapine and lithium), TDM may be used to adjust the dose to individual need and to minimize the risk of dose-related toxicity. Even for drugs with a wide margin of safety, TDM may be helpful in assessing adherence to therapy as a reason for treatment failure. An appreciation of drug metabolism and of pharmacokinetics, the study of the rates of drug absorption, distribution, metabolism and elimination, is essential in understanding the influence of age, sex, other genetic variables, disease, and other parameters on the time course and clinical effect of drugs in the body. The availability of a range of non-isotopic immunoassays compatible with high-throughput clinical chemistry analyzers has meant that certain TDM assays are widely available, but in many cases chromatographic methods (nowadays usually HPLC or LC-MS) have to be used. Whatever technique is used when providing a TDM service, adherence to the principles of quality management (proper method implementation and validation, and adherence to internal quality control and external quality assessment procedures) is essential since treatment decisions may be based on the results.