TY - JOUR T1 - VALIDATION OF (-)-<em>N</em>-3-BENZYL-PHENOBARBITAL AS A SELECTIVE INHIBITOR OF CYP2C19 IN HUMAN LIVER MICROSOMES JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 584 LP - 586 DO - 10.1124/dmd.32.6.584 VL - 32 IS - 6 AU - Xiaoxin Cai AU - Regina W. Wang AU - Richard W. Edom AU - David C. Evans AU - Magang Shou AU - A. David Rodrigues AU - Wensheng Liu AU - Dennis C. Dean AU - Thomas A. Baillie Y1 - 2004/06/01 UR - http://dmd.aspetjournals.org/content/32/6/584.abstract N2 - (-)-N-3-Benzyl-phenobarbital (NBPB) was reported to be a potent and selective inhibitor of CYP2C19. To validate the selectivity of NBPB toward CYP2C19 in human liver microsomes, the inhibitory effects on major cytochrome P450 isoform-specific reactions were evaluated in the present study. In human liver microsomes, NBPB showed potent competitive inhibition on CYP2C19-mediated S-mephenytoin 4′-hydroxylation with an IC50 value of 0.25 μM and Ki value of 0.12 μM, whereas weak inhibition was observed for CYP1A2-, CYP2A6-, CYP2B6-, CYP2C8-, CYP2C9-, CYP2D6-, and CYP3A4-mediated reactions with IC50 values &gt;100, &gt;100, 62, 34, 19, &gt;100, and 89 μM, respectively. Importantly, its selectivity toward CYP2C19 among the CYP2C subfamily was demonstrated. Therefore, NBPB can be used as a potent and selective inhibitor to establish the relative contribution of CYP2C19 for in vitro reaction phenotyping studies. This compound can also serve as a positive control inhibitor of CYP2C19 for routine screening of P450 reversible inhibition when human liver microsomes are used as the enzyme source. The American Society for Pharmacology and Experimental Therapeutics ER -