In vitro biotransformation of SDZ RAD: a new immunosuppressive macrolide in human liver microsomal preparations.
In the present biotransformation study using human in vitro liver samples, metabolites of SDZ RAD were characterized by LC-MS. The major metabolites resulted from single hydroxylation and demethylation pathways and corresponded to the class of first-generation metabolites; 39-O-demethyl-RAD was identified as metabolite. The potential ring-opened degradation product resulting from ester hydrolysis and its dehydrated analogue (seco acid) was detected to comparable amounts in both the incubations and in controls without the presence of NADPH. The direct formation of rapamycin from SDZ RAD could not be detected in this study.
Department of Preclinical Safety, Novartis Pharma AG, Basel, Switzerland.
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Dannecker
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Vickers
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G
Ubeaud
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C
Hauck
D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D000068338:Everolimus; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D008862:Microsomes, Liver / Q000378:metabolism*; D015394:Molecular Structure; D011090:Polyenes / Q000737:chemistry / Q000493:pharmacokinetics*; D011865:Radioisotope Dilution Technique; D020123:Sirolimus / Q000031:analogs & derivatives; D014316:Tritium
D007166:Immunosuppressive Agents; D011090:Polyenes; D014316:Tritium; D000068338:Everolimus; D020123:Sirolimus