Table 1

Ki values and inhibitory patterns of azelastine and its metabolites for human CYP activities1-a

IsoformActivityAzelastineDesmethylazelastine6-Hydroxyazelastine
μM μM μM
CYP2B6BRODND32.6  ± 4.8,1-b uncompetitiveND1-c
CYP2C9 S-WFOH13.9  ± 1.8, competitive15.0  ± 3.1, mixed17.0  ± 4.1, mixed
CYP2C19 S-MPOH21.9  ± 2.2, competitive7.3  ± 1.6, competitive9.3  ± 1.6, competitive
CYP2D6BFOH1.2  ± 0.1, competitive1.5  ± 0.2, competitive3.0  ± 0.5, competitive
CYP3A4TESOH23.7  ± 4.6, competitive13.2  ± 2.3, competitive 1-d
  • 1-a For BROD, desmethylazelastine ranged from 10 to 50 μM.

  • For S-WFOH, azelastine and desmethylazelastine ranged 10 to 50 μM and 6-hydroxyazelastine ranged 20 to 100 μM.

  • For S-MPOH, azelastine, desmethylazelastine, and 6-hydroxyazelastine ranged from 10 to 30, 2 to 10, and 10 to 50 μM, respectively.

  • For BFOH, all inhibitors ranged from 2 to 10 μM.

  • For TESOH, two inhibitors ranged from 10 to 50 μM.

  • For all Ki determination, both the numbers of substrate and inhibitor concentrations were 4.

  • 1-b Data are expressed as mean ± S.E.

  • 1-c ND, not determined.

  • 1-d 6-Hydroxyazelastine interfered with the quantification of 6β-hydroxytestosterone.