title: Pharmacokinetics and biotransformation of the cyclosporine metabolite M-17 in the rabbit.
abstract: 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.
authors.affiliation: Department of Clinical Chemistry, University of Manitoba, Winnipeg, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Copeland
authors.forename: M
authors.initials: M
authors.lastname: Lukowski
authors.forename: R
authors.initials: R
authors.lastname: Yatscoff
authors.forename: J
authors.initials: J
authors.lastname: Thliveris
authors.forename: N
authors.initials: N
authors.lastname: Honcharik
mesh_terms: 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
chemical_list: D003524:Cyclosporins; C051527:cyclosporine metabolite M17