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An inhibitory metabolite leads to dose- and time-dependent pharmacokinetics of (R)-N-{1-[3-(4-ethoxy-phenyl)-4-oxo-3,4-dihydro-pyrido[2,3-d]pyrimidin-2-yl]-ethyl}-N-pyridin-3-yl-methyl-2-(4-trifluoromethoxy-phenyl)-acetamide (AMG 487) in human subjects after multiple dosing.
Tonn GR, Wong SG, Wong SC, Johnson MG, Ma J, Cho R, Floren LC, Kersey K, Berry K, Marcus AP, Wang X, Van Lengerich B, Medina JC, Pearson PG, Wong BK. Tonn GR, et al. Among authors: wong sc, wong bk, wong sg. Drug Metab Dispos. 2009 Mar;37(3):502-13. doi: 10.1124/dmd.108.021931. Epub 2008 Dec 16. Drug Metab Dispos. 2009. PMID: 19088267 Clinical Trial.
Bioactivation of a novel 2-methylindole-containing dual chemoattractant receptor-homologous molecule expressed on T-helper type-2 cells/D-prostanoid receptor antagonist leads to mechanism-based CYP3A inactivation: glutathione adduct characterization and prediction of in vivo drug-drug interaction.
Wong SG, Fan PW, Subramanian R, Tonn GR, Henne KR, Johnson MG, Tadano Lohr M, Wong BK. Wong SG, et al. Among authors: wong bk. Drug Metab Dispos. 2010 May;38(5):841-50. doi: 10.1124/dmd.109.031344. Epub 2010 Jan 25. Drug Metab Dispos. 2010. PMID: 20100816
Sequential metabolism of AMG 487, a novel CXCR3 antagonist, results in formation of quinone reactive metabolites that covalently modify CYP3A4 Cys239 and cause time-dependent inhibition of the enzyme.
Henne KR, Tran TB, VandenBrink BM, Rock DA, Aidasani DK, Subramanian R, Mason AK, Stresser DM, Teffera Y, Wong SG, Johnson MG, Chen X, Tonn GR, Wong BK. Henne KR, et al. Among authors: wong bk, wong sg. Drug Metab Dispos. 2012 Jul;40(7):1429-40. doi: 10.1124/dmd.112.045708. Epub 2012 Apr 19. Drug Metab Dispos. 2012. PMID: 22517972
102 results