Table 3

Contribution of CYP1A2, CYP2D6, and CYP3A4 to azelastine N-demethylation in human liver microsomes by prediction methods 1 and 2

Human LiverHLG1HLG4HLG6HLG7HLG10HLG11
pmol/min/mg
vHL 28.237.713.729.653.912.2
Content pmol/mg
 CYP1A27117351259730
 CYP2D613041116
 CYP3A495129946217752
Prediction method 1 using B-lymphoblast pmol/min/mg (% contribution) cells
 vCYP1A2 0  (0)0  (0)0  (0)0  (0)0  (0)0  (0)
 vCYP2D6 2.7  (9.5)0  (0)0.8  (6.0)2.3  (7.6)0.2  (0.4)1.2  (10.1)
 vCYP3A4 0.9  (3.0)1.2  (3.1)0.8  (6.2)0.6  (1.9)1.6  (3.0)0.5  (3.8)
Prediction method 1 using baculovirus-infected insect cells pmol/min/mg (% contribution)
 vCYP1A2 0.7  (2.3)11.0  (29.2)3.3  (24.0)11.8  (39.7)9.1  (16.9)2.8  (23.1)
 vCYP2D6 8.5  (30.2)0  (0)2.6  (19.2)7.2  (24.4)0.7  (1.2)3.9  (32.3)
 vCYP3A4 (withoutb 5)9.5  (33.6)12.9  (34.2)9.4  (68.7)6.2  (20.9)17.7  (32.8)5.2  (42.6)
 vCYP3A4 (with b 5)7.3  (25.9)9.9  (26.4)7.2  (52.9)4.8  (16.1)13.6  (25.3)4.0  (32.8)
Prediction method 2 using B-lymphoblast cells pmol/min/mg (% contribution)
 vCYP1A2 3-a
 vCYP2D6 2.4  (8.4)0  (0)0.7  (5.4)2.0  (6.8)0.2  (0.3)1.1  (9.0)
 vCYP3A4 0.7  (2.6)1.0  (2.7)0.7  (5.4)0.5  (1.6)1.4  (2.6)0.4  (3.3)
Prediction method 2 using baculovirus-infected insect cells pmol/min/mg (% contribution)
 vCYP1A2 0.9  (3.2)15.2  (40.4)4.6  (33.3)16.3  (54.9)12.6  (23.4)3.9  (32.0)
 vCYP2D6 6.7  (23.8)0  (0)2.1  (15.1)5.7  (19.2)0.5  (1.0)3.1  (25.4)
 vCYP3A4 (withoutb 5)5.7  (20.1)7.7  (20.4)5.6  (41.0)3.7  (12.5)10.6  (19.6)3.1  (25.5)
 vCYP3A4 (with b 5)8.1  (28.7)11.0  (29.2)8.0  (58.7)5.3  (17.9)15.1  (28.0)4.4  (36.4)

Prediction methods 1 and 2 were described in Materials and Methods.

  • ↵3-a , Not determined.