The evolution of therapeutic immunosuppression and the potential impact of drug concentration monitoring.
The major goal of immunosuppressive development is improved selectivity of the drug's inhibitory action against T and B cell-mediated as opposed to nonspecific granulocyte-, monocyte-, and macrophage-mediated resistance. This enterprise demands increased knowledge of alloantigen-induced stimulation, signal transduction, and/or maturation pathways of T and B cells. A second approach seeks to harness synergistic combinations of existent albeit not entirely specific agents in order to potentiate immunosuppressive and minimize drug-induced toxicity by using subtherapeutic doses of each agent. The development of synergistic regimens demands not only good estimates of drug effects but also precise measures of drug concentrations because therapeutic effects do not reflect administered doses. Therefore, until immunologic assays are available to assess biologic effects and until drug receptor concentrations can be estimated, there is an increasing need for therapeutic drug monitoring (TDM) to afford reliable surrogates that predict the clinical outcomes of therapeutic regimens. The application of mathematical models such as the median effect analysis provides a quantitative tool for this enterprise. Thus, TDM methodologies seem to present the best available approach to develop secure algorithms for clinical immunosuppression.
Kahan
B D
BD
Division of Immunology and Organ Transplantation, University of Texas Medical School, Houston 77030, USA.
D016903:Drug Monitoring / Q000266:history*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D049673:History, 20th Century; D006801:Humans; D007165:Immunosuppression Therapy / Q000266:history*; D007166:Immunosuppressive Agents / Q000266:history
D007166:Immunosuppressive Agents