PT - JOURNAL ARTICLE AU - Markus Zollinger AU - Claudia Sayer AU - Robert Dannecker AU - Walter Schuler AU - Richard Sedrani TI - The Macrolide Everolimus Forms an Unusual Metabolite in Animals and Humans: Identification of a Phosphocholine Ester AID - 10.1124/dmd.108.020651 DP - 2008 Aug 01 TA - Drug Metabolism and Disposition PG - 1457--1460 VI - 36 IP - 8 4099 - http://dmd.aspetjournals.org/content/36/8/1457.short 4100 - http://dmd.aspetjournals.org/content/36/8/1457.full SO - Drug Metab Dispos2008 Aug 01; 36 AB - The immunosuppressant macrolide everolimus was found to be metabolized in animals and humans to a phosphocholine ester (ATG181), a hitherto unknown type of conjugate in xenobiotic metabolism. The structure of ATG181 was elucidated by mass spectrometry and confirmed by synthesis. ATG181 was among the most prominent metabolites of everolimus in rat, monkey, and human blood and was found also in various tissues of the rat, whereas no ATG181 was identified in the urine and feces of the species investigated. The metabolite showed binding to FK506 binding protein with a 2- to 3-fold higher affinity than everolimus. However, ATG181 exhibited only marginal in vitro immunosuppressive activity and is therefore very unlikely to contribute in a relevant manner to the immunosuppressive effect of everolimus. The American Society for Pharmacology and Experimental Therapeutics