Toxicodynamic effects of ciclosporin are reflected by metabolite profiles in the urine of healthy individuals after a single dose.

British Journal of Clinical Pharmacology
Jost KlawitterUwe Christians

Abstract

WHAT IS ALREADY KNOWN ABOUT THE SUBJECT * Ciclosporin's nephrotoxicity initially targets the proximal tubule and is, at least in part, driven by increased formation of oxygen radicals. * (1)H-nuclear magnetic resonance spectroscopy (NMR)- and mass spectrometry (MS)-based biochemical profiling (metabolomics) allows for the sensitive detection of metabolite pattern changes in urine. * In systematic studies in rats we showed that ciclosporin caused urine metabolite pattern changes typical for proximal tubule damage and that these pattern changes seemed to be more sensitive than established clinical kidney function markers such as serum creatinine concentrations. WHAT THIS PAPER ADDS * This study showed that urine metabolite pattern changes as assessed by (1)H-NMR and HPLC-MS are sensitive enough to detect the effect of ciclosporin as early as 4 h after a single oral dose. * In our previous rat studies, changes in urine metabolite pattern in response to ciclosporin translated into healthy humans, indicating the involvement of the same toxicodynamic mechanisms. * The results provide proof of concept for further development of this combination molecular marker strategy into diagnostic tools for the detection and monitoring of drug ne...Continue Reading

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Citations

Dec 4, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·Donald G RobertsonMichael D Reily
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Apr 9, 2015·Human & Experimental Toxicology·J D XuH Lu
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