Pharmacokinetics and biotransformation of the cyclosporine metabolite M-17 in the rabbit.
The monohydroxylated cyclosporine (CsA) metabolite M-17 was isolated from bile of human liver transplant recipients by preparative HPLC. The structure and purity of the metabolite were confirmed by fast atom bombardment-mass spectroscopy and proton NMR. The isolated metabolite was administered iv to three rabbits at a dose of 1.0 mg/kg with the following mean pharmacokinetic parameters being determined: half-life (t1/2B) 2.22 hr, volume of distribution (Vss) 1.44 liters/kg, and clearance 11.07 ml/min/kg. These are not significantly different from those obtained for CsA. In bile and urine obtained from rabbits administered M-17, the CsA metabolites M-8, M-18, and M-26 were found, indicating that M-17 is further metabolized. The latter data support the proposed biotransformation pathways for M-17.
Copeland
K
K
Department of Clinical Chemistry, University of Manitoba, Winnipeg, Canada.
Lukowski
M
M
Yatscoff
R
R
Thliveris
J
J
Honcharik
N
N
D000818:Animals; D001646:Bile / Q000378:metabolism; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D003524:Cyclosporins / Q000378:metabolism* / Q000493:pharmacokinetics; D007016:Hypophysectomy; D016031:Liver Transplantation; D009682:Magnetic Resonance Spectroscopy; D011817:Rabbits
D003524:Cyclosporins; C051527:cyclosporine metabolite M17