TY - JOUR T1 - Role of Human CYP2B6 in <em>S</em>-Mephobarbital<em>N</em>-Demethylation JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 1429 LP - 1433 VL - 27 IS - 12 AU - Kaoru Kobayashi AU - Seiji Abe AU - Miki Nakajima AU - Noriaki Shimada AU - Masayoshi Tani AU - Kan Chiba AU - Toshinori Yamamoto Y1 - 1999/12/01 UR - http://dmd.aspetjournals.org/content/27/12/1429.abstract N2 - The role of cytochrome P-450s (CYPs) inS-mephobarbital N-demethylation was investigated by using human liver microsomes and cDNA-expressed CYPs. Among the 10 cDNA-expressed CYPs studied (CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4), only CYP2B6 could catalyze S-mephobarbitalN-demethylation. The apparentKm values of human liver microsomes forS-mephobarbital N-demethylation were close to that of cDNA-expressed CYP2B6 (about 250 μM). TheN-demethylase activity of S-mephobarbital in 10 human liver microsomes was strongly correlated with immunodetectable CYP2B6 levels (r = 0.920,p &lt; .001). Orphenadrine (300 μM), a CYP2B6 inhibitor, inhibited the N-demethylase activity ofS-mephobarbital in human liver microsomes to 29% of control activity. Therefore, it appears that CYP2B6 mainly catalyzesS-mephobarbital N-demethylation in human liver microsomes. The American Society for Pharmacology and Experimental Therapeutics ER -