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Pharmacology of cyclosporine and tacrolimus

Karen Hardinger, PharmD, BCPS
Colm C Magee, MD, MPH, FRCPI
Section Editors
Daniel E Furst, MD
Daniel C Brennan, MD, FACP
Deputy Editor
Albert Q Lam, MD


Cyclosporine and tacrolimus selectively inhibit calcineurin, thereby impairing the transcription of interleukin (IL)-2 and several other cytokines in T lymphocytes. Calcineurin inhibitors have been mainstays of immunosuppression in solid organ transplantation for over three decades.

Cyclosporine and tacrolimus are occasionally used in the treatment of various immune-mediated diseases. However, concerns about their long-term toxicity (especially renal dysfunction and hypertension) and the availability of newer biologic agents have restricted the use of cyclosporine and tacrolimus to patients who have not responded to conventional treatment. The renal toxicity of these agents is reviewed in detail separately. (See "Cyclosporine and tacrolimus nephrotoxicity".)

The pharmacology of cyclosporine and tacrolimus is reviewed here. The efficacy and use of these agents in specific conditions, including organ transplantation and immune-mediated diseases, are discussed separately in the topic reviews addressing the treatment of each disorder. (See appropriate topic reviews.)


Cyclosporine is a lipophilic cyclic peptide of 11 amino acids, while tacrolimus is a macrolide antibiotic. Both drugs have been isolated from fungi and possess similar suppressive effects on cell-mediated and humoral immune responses.

Both drugs bind with high affinity to a family of cytoplasmic proteins present in most cells: cyclophilins for cyclosporine, and FK-binding proteins for tacrolimus. The drug-receptor complex specifically and competitively binds to and inhibits calcineurin, a calcium- and calmodulin-dependent phosphatase [1-4]. This process inhibits the translocation of a family of transcription factors (NF-AT), leading to reduced transcriptional activation of cytokine genes for interleukin (IL)-2, tumor necrosis factor (TNF)-alpha, IL-3, IL-4, CD40L, granulocyte-macrophage colony-stimulating factor, and interferon-gamma [1,2,5,6]. Ultimately, proliferation of T lymphocytes is reduced.

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Literature review current through: Nov 2017. | This topic last updated: Mar 31, 2017.
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