藥學科技報告
步驟五-1：輸入你要找的東西，下面可以依你不同的需求縮小搜尋範圍，
可以選擇(1)發行的年份(2)文件的格式(3)語言(4)作者的名稱(5)公司名稱
步驟五-3：搜尋的第一階段會出現許多中搜尋方法，
例如我搜尋的Topic是”The Metabolism of Methadone”
步驟六-1：搜尋好了之後，SciFinder還會幫你最進一步的分類，你還可以依居你
所需要的東西的細節，像是Substances或Reactions做進一步的搜尋
步驟七：以下為搜尋”
The Metabolism of Methadone”的第一篇文著的內
容
• Stereo-selective of by human liver microsomes and cDNA-expressed cytochrome P450s: a reconciliation
• Chang, Yan; Fang, Wenfang B.; Lin, Shen-Nan; Moody, David E.
• In vitro metab. of was investigated in cytochrome P 450 (CYP) supersomes and phenotyped
human liver microsomes (HLMs) to reconcile past findings on CYP involvement in stereo-selective metab. of . Racemic was used for incubations; (R)- and (S)- turnover and (R)- and (S)-EDDP formation were detd. using chiral liq. chromatog.-tandem mass spectrometry. CYP supersome activity for use and EDDP formation ranked CYP2B6 > 3A4 > 2C19 > 2D6 > 2C18, 3A7 > 2C8, 2C9, 3A5. After abundance scaling, CYP3A4, 2B6 and 2C19 accounted for 63-74, 12-32 and 1.4-14% of resp. activity. CYP2B6, 2D6 and 2C18 demonstrated a preference for (S)-EDDP
formation; CYP2C19, 3A7 and 2C8 for (R)-EDDP; 3A4 none. Correlation anal. with 15 HLMs supported the involvement of CYP2B6 and 3A. The significant correlation of S/R ratio with CYP2B6 activity confirmed its stereo-selectivity. CYP2C19 and 2D6 inhibitors and monoclonal antibody (mAb) did not inhibit EDDP formation in HLM. Chem. and mAb inhibition of CYP3A in high 3A activity HLM reduced EDDP formation by 60-85%; inhibition of CYP2B6 in 2B6 high-activity HLM reduced (S)-EDDP formation by 80% and (R)-EDDP formation by 55%. Inhibition changed metab. in a stereo-selective manner. When CYP3A was inhibited, 2B6 mediated EDDP formation predominated; S/R stereo-selectivity increased. When 2B6 was inhibited (S)-EDDP formation fell and stereo-selectivity decreased. The results confirmed the primary roles of CYPs 3A4 and 2B6 in metab.; CYP2C8 and 2C9 did not appear involved; 2C19 and 2D6 have minimal roles. CYP2B6 is the primary determinant of stereo-selective metab.; stereo-selective inhibition might play a role in varied plasma concns. of the two enantiomers.
