Personalized Minimal Effective Concentration Therapy

Abstract

It has been recognized for literally centuries that patients should be given only the amount of medication necessary to treat disease(s) or relieve symptoms. It is also well known that this amount can vary greatly between patients or even over time in the same patient. The ability to identify this amount, that is, to "personalize" dosing, requires a reliable measure of a patient's response to treatment. The development of analytical methods for the accurate measurement of pharmacologically meaningful drug concentrations in physiologic fluids, combined with mathematical methods for reliable prediction of how dosing changes affect these concentrations, has led to the development of therapeutic drug management (TDM) for more effective individualization of dosing. Using TDM, clinicians modify dosing to achieve concentrations or exposures (ie, AUC) found to be effective in patients with similar clinical attributes and conditions. These concentrations, called therapeutic (or target) concentrations or exposure ranges (TRs), are specific to both disease/condition and patient population. TDM is routinely used by many clinicians to adjust dosing of a wide range of medications for maximal efficacy and limited toxicity, thereby improving clinical outcomes. Failure to properly perform TDM or to appreciate the limitations of TDM have, however, contributed to the delayed acceptance of TDM by clinicians. This Commentary briefly discusses the limitations and the benefits of TR-guided TDM, and then discusses immunosuppressant drugs and anticancer medications as examples of drugs that require clinicians to change their prescribing practices from giving all patients the same or maximal tolerated doses, to instead adjusting individual doses to achieve minimal effective concentrations identified using circulating tumor- or graft-derived DNA or copy number instability rather than published TRs.

Keywords: Immunosuppressants; Liquid biopsy; Minimal effective concentrations; Oncology; Personalized therapy.