Identification and in vitro immunosuppressive activity of a SDZ-IMM-125 metabolite isolated from phenobarbital-induced rabbit liver microsomes.
1. A metabolite of D-serine-cyclosporine A has been isolated from phenobarbital induced rabbit liver microsomes using hplc. 2. This metabolite was identified by FAB, electrospray mass spectrometry as well as nmr spectroscopy and is the result of metabolism of the vinylic methyl group of the 9-carbon amino acid unique to the cyclosporins, the first amino acid of this cyclic undecapeptide. This metabolite exhibits a significantly lower immunosuppressive activity than IMM-125 and CsA.
Dieden
R
R
Department of Pharmaceutical Sciences, Laboratory of Mass Spectrometry, Brussels, Belgium.
Verbeeck
R K
RK
Maton
N
N
Latinne
D
D
Lhoëst
G J
GJ
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003524:Cyclosporins / Q000378:metabolism* / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology*; D011817:Rabbits; D016339:Spectrometry, Mass, Fast Atom Bombardment
D003524:Cyclosporins; C082770:IMM 125; D007166:Immunosuppressive Agents; D010634:Phenobarbital