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In Vitro Metabolism of Leflunomide by Mouse and Human Liver Microsomes

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Leflunomide was found to be metabolized predominantly to A77-1726 and two novel hydroxylated metabolites, M1 and M2, in microsomes while A77-1726 was only biotransformed to M1. M1 and M2 were proposed to be the hydroxylated α-cyanoenol form of A77-1726 and the hydroxylated 5 methyl-isoxazole form of leflunomide, respectively.





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Keywords: A77-1726; Leflunomide; QTOFMS; UPLC; metabolic profiling; microsomes

Document Type: Research Article

Publication date: December 1, 2007

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  • Drug Metabolism Letters publishes short papers on major advances in all areas of drug metabolism and disposition. The emphasis will be on publishing quality papers very rapidly. Letters will be processed rapidly by taking full advantage of the Internet technology for both the submission and review of manuscripts. The journal covers the following areas:

    In vitro systems including CYP-450; enzyme induction and inhibition; drug-drug interactions and enzyme kinetics; pharmacokinetics, toxicokinetics, species scaling and extrapolations; P-glycoprotein and transport carriers; target organ toxicity and interindividual variability; drug metabolism and disposition studies; extrahepatic metabolism; phase I and phase II metabolism; recent developments for the identification of drug metabolites, reactive intermediate and glutathione conjugates.
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