Isolation and identification of a novel human metabolite of cyclosporin A: dihydro-CsA M17.
A novel metabolite of cyclosporin A was observed in human blood and urine. An analytical sample of this metabolite was isolated from human urine and the structure was determined to be (8-hydroxy-6,7-dihydro-MeBMT1) cyclosporin based on the 1H-NMR, 13C-NMR, FAB-MS, and HPLC characteristics of the biological sample as well as by comparison with a synthetically derived authentic sample. The significance of this metabolite in terms of the pathway by which cyclosporin A is metabolized is discussed.
Meier
G P
GP
Department of Medicinal Chemistry, School of Pharmacy, University of Washington, Seattle 98195.
Park
S B
SB
Yee
G C
GC
Gmur
D J
DJ
D002851:Chromatography, High Pressure Liquid; D003524:Cyclosporins / Q000378:metabolism* / Q000652:urine; D004064:Digestive System / Q000378:metabolism / Q000382:microbiology; D006801:Humans; D006900:Hydroxylation; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry
D003524:Cyclosporins; C064083:8-hydroxy-6,7-dihydro-(4-(2-butenyl)-4,N-dimethylthreonine)cyclosporin; C054666:dihydrocyclosporin A