The isolation, structural characterization, and immunosuppressive activity of cyclosporin G (NVa2-cyclosporine) metabolites.
Seven cyclosporin G metabolites were isolated by high-performance liquid chromatography from the urine of normal subjects receiving the drug. The structure and purity of the metabolites were assessed by fast atom bombardment/mass spectroscopy, by proton nuclear magnetic resonance (NMR), and by 13C-NMR. The structural modifications of the cyclosporin G metabolites consisted primarily of hydroxylation and demethylation, as is the case for cyclosporin A metabolites. The immunosuppressive activities of the metabolites were tested in three separate in vitro systems: a primary and secondary mixed lymphocyte system, as well as a mitogen stimulated system. In general, the metabolites have immunosuppressive activity of less than 10% of cyclosporin G. The significance of these findings in relation to the therapeutic monitoring of cyclosporin G is discussed.
Copeland
K R
KR
Department of Clinical Chemistry, Health Sciences Clinical Research Centre, Winnipeg, Manitoba, Canada.
Yatscoff
R W
RW
D002851:Chromatography, High Pressure Liquid; D016572:Cyclosporine; D003524:Cyclosporins / Q000737:chemistry / Q000276:immunology / Q000302:isolation & purification* / Q000652:urine; D006801:Humans; D007166:Immunosuppressive Agents / Q000737:chemistry* / Q000276:immunology / Q000302:isolation & purification / Q000652:urine; D008214:Lymphocytes / Q000276:immunology; D016339:Spectrometry, Mass, Fast Atom Bombardment
D003524:Cyclosporins; D007166:Immunosuppressive Agents; C045571:cyclosporin G; D016572:Cyclosporine