Table 3

Effect of known P450 inhibitors on the lactonization and oxidation of AVA, CVA and RVA in human hepatocytes

SubstrateMetabolite% of Control (Mean ± S.D., n = 3)
1 μM Ketoconazole20 μM Sulfaphenazole
AVAAV157 ± 3118 (n = 2)
Hydroxy AVA - 130 ± 7108 (n = 2)
Hydroxy AVA - 218 ± 1293 (n = 2)
CVACV95 ± 2107 ± 20
Hydroxy CVA80 ± 388 ± 19
Demethylated CVA51 ± 799 ± 5
RVARV96 ± 699 (n = 2)
Demethylated RVA53 ± 765 (n = 2)

Results are expressed as percentage of control values (means ± S.D.,n = 3 hepatocyte preparations) and were obtained following coincubation of statins (20 μM) and inhibitors at 37°C for 60 min (AVA and CVA) or 120 min (RVA) with human hepatocytes (3 × 106 cells/ml).