TABLE 2

Evaluation of the selectivity of azamulin toward CYP3A4 in suspended human hepatocytes: determination of its inhibitory effect on phase II enzymes, aldehyde oxidase, FMO, and CES1

SubstrateEnzymeReaction MonitoredPercentage of Inhibitiona
1′-HydroxymidazolamUGT1A4, 2B4, 2B7Parent disappearance26 (14)
4′-HydroxycoumarinUGTs, SULTsParent disappearance4 (8)
PhthalazineAldehyde oxidaseParent disappearance−0.6 (6)
CimetidineFMOMetabolite formation13 (13)
RanitidineFMOMetabolite formation24 (4)
CDP323CES1Metabolite formation−7 (23)
ImipramineUGT1A4Metabolite formation−6 (13)
5-HydroxytryptopholUGT1A6Parent disappearance−2 (13)
PropofolUGT1A9Metabolite formation−3 (0.1)
NaloxoneUGT2B7Metabolite formation29 (5.4)
S-OxazepamUGT2B15Metabolite formation31 (8.4)
  • a Mean of three independent values (S.E.M.).