期刊
BIOLOGICAL & PHARMACEUTICAL BULLETIN
卷 41, 期 1, 页码 106-114出版社
PHARMACEUTICAL SOC JAPAN
DOI: 10.1248/bpb.b17-00709
关键词
induced pluripotent stem cell; hepatocyte; fentanyl; metabolism
资金
- Japan Society for the Promotion of Science (JSPS) KAKENHI [15K08895]
- Grants-in-Aid for Scientific Research [15K08895] Funding Source: KAKEN
To evaluate the capability of human-induced pluripotent stem cell-derived hepatocytes (h-iPS-HEP) in drug metabolism, the profiles of the metabolites of fentanyl, a powerful synthetic opioid, and acetylfentanyl, an N-acetyl analog of fentanyl, in the cells were determined and analyzed. Commercially available h-iPS-HEP were incubated with fentanyl or acetylfentanyl for 24 or 48h. After enzymatic hydrolysis, the medium was deproteinized with acetonitrile, then analyzed by LC/MS. Desphenethylated metabolites and some hydroxylated metabolites, including 4'-hydroxy-fentanyl and beta-hydroxy-fentanyl, were detected as metabolites of fentanyl and acetylfentanyl in the medium. The main metabolite of fentanyl with h-iPS-HEP was the desphenethylated metabolite, which was in agreement with in vivo results. These results suggest that h-iPS-HEP may be useful as a tool for investigating drug metabolism.
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