PT  - JOURNAL ARTICLE
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
TI  - VALIDATION OF (-)-<em>N</em>-3-BENZYL-PHENOBARBITAL AS A SELECTIVE INHIBITOR OF CYP2C19 IN HUMAN LIVER MICROSOMES
AID  - 10.1124/dmd.32.6.584
DP  - 2004 Jun 01
TA  - Drug Metabolism and Disposition
PG  - 584--586
VI  - 32
IP  - 6
4099  - http://dmd.aspetjournals.org/content/32/6/584.short
4100  - http://dmd.aspetjournals.org/content/32/6/584.full
SO  - Drug Metab Dispos2004 Jun 01; 32
AB  - (-)-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 >100, >100, 62, 34, 19, >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