Cellular pharmacodynamics of immunosuppressive drugs for individualized medicine.
The therapeutic effects of immunosuppressive drugs are known to deviate largely between patients, but efficient strategies for the differentiation of patients who show clinical resistance to immunosuppressive therapies have not been established. Accordingly, a considerable number of patients receive treatment with immunosuppressive drugs despite the onset of serious side effects and poor responses. Cellular pharmacodynamics of immunosuppressive drugs in vitro using peripheral lymphocytes derived from each patient, an attractive way to distinguish resistant patients, is respected and has been applied to the carrying out of individualized immunosuppressive therapy. In this article, I summarize experimental procedures for assaying immune cell responses to immunosuppressive drugs in vitro, and highlight the relationship between cellular sensitivity to immunosuppressive drugs and the therapeutic efficacy of drugs in organ transplantation and several immunological disorders. I will also overview the molecular mechanisms and genetic bases for cellular and clinical resistance to immunosuppressive drugs. Lastly, the future clinical prospects for the application of in vitro drug sensitivity tests for "patient-tailored" immunosuppressive therapies are discussed.
Hirano
Toshihiko
T
Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan. hiranot@ps.toyaku.ac.jp
D002478:Cells, Cultured; D004351:Drug Resistance; D006801:Humans; D007154:Immune System Diseases / Q000188:drug therapy; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology; D015166:Monitoring, Immunologic / Q000379:methods; D009404:Nephrotic Syndrome / Q000188:drug therapy; D016377:Organ Transplantation; D010597:Pharmacogenetics
D007166:Immunosuppressive Agents