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- W190041310 abstract "A new series of NNRTIs with substituted or unsubstituted pyridine has been developed, and members of this series have demonstrated potent activity against NNRTI-resistant virus. In this study, both in vitro microsomal stability assay and in vivo animal pharmacokinetics study were conducted for selected NNRTIs in order to establish the in vitro-in vivo correlations. There was a good correlation for the substituted pyridine analogs, but for the unsubstituted pyridine analogs, the in vivo clearance was under-predicted in vitro. We investigated the metabolic pathways of several substituted pyridine analogs and one unsubstituted pyridine analog. The hydroxylation on the ring and N-hydroxylation of the amino group were found to be the major metabolic pathways for the substituted pyridine analogs. However, for the unsubstituted pyridine analog, N-oxide formation was the single most important metabolic pathway. This pathway was under-represented in the liver microsomes, which indicates that the N-oxide formation was likely catalyzed by non-P450 enzyme systems. Further investigations are underway to identify the enzyme system that is responsible for the N-oxide formation on the unsubstituted pyridines. This research is supported by Gilead Sciences, Inc." @default.
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- W190041310 date "2007-01-01" @default.
- W190041310 modified "2023-10-07" @default.
- W190041310 title "Metabolism of substituted vs. unsubstituted pyridine analogs of NNRTIs" @default.
- W190041310 doi "https://doi.org/10.1096/fasebj.21.6.lb78-c" @default.
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