Pharmacokinetics and biotransformation of the cyclosporine metabolite M-17 in the rabbit |
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| Authors: | K Copeland M Lukowski R Yatscoff J Thliveris N Honcharik |
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| Institution: | Department of Clinical Chemistry, University of Manitoba, Winnipeg, Canada. |
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| 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. |
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