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Human hepatic metabolism of the anxiolytic agent, RWJ-51521 — API-MS/MS identification of metabolites

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Summary

The In vitro metabolism of the anxiolytic agent, RWJ-51521 was conducted after incubation with human hepatic S9 fraction in the presence of an NADPH-generating system. Unchanged RWJ-51521 (30% of the sample) and a total of 11 metabolites were profiled, quantified, and tentatively identified on the basis of API (ionspray)-MS/MS data. The 4 proposed metabolic pathways for RWJ-51521 are: (1) N/O-dealkylation, (2) phenylhydroxylation, (3) pyrido-oxidation, and (4) dehydration. Pathway 1 formed 2 major and 3 minor N/O-desalkyl metabolites (Ml & M3,50%) and in conjunction with pathway 4, formed 2 moderate dehydrated metabolites (M4 & M5, 14%). Pathways 2 and 3 alone, and in conjunction with pathway 4, produced 4 minor metabolites (each ≤2%). RWJ-51521 is extensively metabolized in human hepatic S9 fraction.

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  1. Johnson & Johnson Pharmaceutical Research & Development, L.L.C., Welsh & McKean Roads, 19477, Spring House, PA, USA

    W. N. Wu, L. A. McKown & A. B. Reitz

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  1. W. N. Wu
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  2. L. A. McKown
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  3. A. B. Reitz
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Wu, W.N., McKown, L.A. & Reitz, A.B. Human hepatic metabolism of the anxiolytic agent, RWJ-51521 — API-MS/MS identification of metabolites. European Journal of Drug Metabolism and Pharmacokinetics 29, 257–262 (2004). https://doi.org/10.1007/BF03190608

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