CYP3A5 gene variation influences cyclosporine A metabolite formation and renal cyclosporine disposition.

ABSTRACT:

Background

Higher concentrations of AM19 and AM1c9, secondary metabolites of cyclosporine A (CsA), have been associated with nephrotoxicity in organ transplant patients. The risk of renal toxicity may depend on the accumulation of CsA and its metabolites in the renal tissue. We evaluated the hypothesis that CYP3A5 genotype, and inferred enzyme expression, affects systemic CsA metabolite exposure and intrarenal CsA accumulation.

Methods

An oral dose of CsA was administered to 24 healthy volunteers who were selected based on their CYP3A5 genotype. CsA and its six main metabolites in whole blood and urine were measured by liquid chromatography-mass spectometry. In vitro incubations of CsA, AM1, AM9, and AM1c with recombinant CYP3A4 and CYP3A5 were performed to evaluate the form

SUBMITTER: Zheng S 

PROVIDER: S-EPMC3604156 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature