In vitro metabolism of the analgesic agent, tramadol-N-oxide, in mouse, rat, and human
European Journal of Drug Metabolism and Pharmacokinetics, ISSN: 0378-7966, Vol: 27, Issue: 3, Page: 193-197
2002
- 7Citations
- 6Captures
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Metrics Details
- Citations7
- Citation Indexes7
- CrossRef6
- Captures6
- Readers6
Article Description
Tramadol-N-oxide (TNO, RWJ-38705) is a new analgesic agent, which is believed to produce its analgesic effect following metabolic conversion to tramadol. In the present study, API ionspray-MS and MS/MS techniques were used to profile the in vitro metabolism of TNO in mouse, rat, and human hepatic S9 fractions in the presence of an NADPH generating system. Unchanged TNO represented 60, 24, and 26% of the sample in mouse, rat, and human, respectively. Tramadol, and seven other metabolites were profiled and tentatively identified on the basis of MS analysis and by comparison to synthetic reference samples. TNO metabolites were formed via four Phase I reactions: (1) N-oxide reduction, (2) O-demethylation, (3) N-demethylation, and (4) cyclohexylhydroxylation. TNO was found to be substantially metabolized in hepatic S9 from all three species. The metabolism of TNO to tramadol via N-oxide reduction was greater in rat and human than in mouse.
Bibliographic Details
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=0036655698&origin=inward; http://dx.doi.org/10.1007/bf03190457; http://www.ncbi.nlm.nih.gov/pubmed/12365201; http://link.springer.com/10.1007/BF03190457; http://www.springerlink.com/index/10.1007/BF03190457; http://www.springerlink.com/index/pdf/10.1007/BF03190457; https://dx.doi.org/10.1007/bf03190457; https://link.springer.com/article/10.1007/BF03190457
Springer Science and Business Media LLC
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