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Metabolic Pathway of Cyclosporine A and Its Correlation with Nephrotoxicity

[ Vol. 20 , Issue. 2 ]


Qinghua Wu* and Kamil Kuca*   Pages 84 - 90 ( 7 )


Cyclosporine A (CsA) is widely used for organ transplantation and autoimmune disorders. However, CsA nephrotoxicity is a serious side effect that limits the clinical use of CsA. Notably, the metabolism of CsA has a close relationship with this disease in renal-transplant patients. The major metabolic pathways of CsA in humans are hydroxylation (AM1 and AM9) and N-demethylation (AM4N). Normally, these metabolites are relatively less toxic than CsA. However, the metabolism of CsA in the kidneys is much weaker than that in the liver, which explains why CsA is so toxic to the kidneys. CYP3A families, especially CYP3A4 and CYP3A5, play an important role in the biotransformation of CsA. Moreover, increased lines of evidence show that some metabolites (including AM19) associate directly with nephrotoxicity in CsA-treated organ-transplant patients. Therefore, it is important to understand the metabolic profiles of CsA in humans, especially in renal-transplant patients. However, the metabolic pathways of CsA and its metabolizing enzymes have rarely been comprehensively reviewed. Therefore, in this review, we have summarized the specific metabolic profiles of CsA in humans, especially renal-transplant patients. Moreover, the specific metabolizing enzymes and the potential roles that CsA metabolism plays in CsA nephrotoxicity were summarized and discussed. We hope that this review will help to further understand the metabolic activities of CsA in renal-transplant patients and cast some light on the mechanisms of CsA nephrotoxicity.


Cyclosporine A, nephrotoxicity, metabolism, metabolic pathways, metabolizing enzymes, renal-transplant patients.


Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove, Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove

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