Table 4

Contribution of CYP1A2, CYP2D6, and CYP3A4 to azelastine N-demethylation in human liver microsomes by prediction methods 3 to 5

Human LiverHLG1HLG4HLG6HLG7HLG10HLG11
μl/min/nmol CYP
CLHL 72.166.947.242.591.238.0
Prediction method 3
 RAFv, CYP1A2 0.0050.0970.0440.1180.0870.073
 RAFv, CYP2D6 0.0200.0020.0060.0130.0020.012
 RAFv, CYP3A4 0.2470.2150.1810.1090.2660.054
μl/min/nmol CYP (% contribution)
 CLCYP1A2 0.6  (0.9)12.7  (19.1)5.7  (12.1)15.5  (36.6)11.4  (12.5)9.5  (25.1)
 CLCYP2D6 15.3  (21.2)1.3  (1.9)4.4  (9.3)10.0  (23.4)1.9  (2.1)8.8  (23.2)
 CLCYP3A4 21.6  (29.9)18.7  (28.0)15.8  (33.5)9.5  (22.3)23.2  (25.4)4.7  (12.4)
Prediction method 4
 RAFvmax, CYP1A2 0.0050.1110.0320.1320.0820.109
 RAFvmax, CYP2D6 0.0740.0250.0600.0480.0180.083
 RAFvmax, CYP3A4 0.5840.6320.6380.3131.0700.240
μl/min/nmol CYP (% contribution)
 CLCYP1A2 0.6  (0.9)14.6  (21.8)4.2  (8.9)17.3  (40.8)10.7  (11.7)14.3  (37.6)
 CLCYP2D6 56.4  (78.2)19.0  (28.5)45.7  (96.9)36.6  (86.0)13.7  (15.0)63.2  (166.4)
 CLCYP3A4 50.9  (70.5)55.0  (82.3)55.6  (117.7)27.3  (64.1)93.2  (102.2)20.9  (55.0)
Prediction method 5
 RAFCL, CYP1A2 0.0010.0120.0200.0130.0190.024
 RAFCL, CYP2D6 0.0350.0010.0110.0250.0040.014
 RAFCL, CYP3A4 0.5430.7800.4110.2390.9830.320
μl/min/nmol CYP (% contribution)
 CLCYP1A2 0.2  (0.2)1.6  (2.4)2.6  (5.4)1.7  (3.9)2.6  (2.8)3.2  (8.4)
 CLCYP2D6 26.3  (36.5)0.9  (1.4)8.0  (17.0)19.2  (45.1)3.0  (3.3)10.5  (27.6)
 CLCYP3A4 47.3  (65.6)68.0  (101.6)35.8  (75.9)20.8  (48.9)85.6  (93.9)27.9  (73.4)

Prediction methods 3 to 5 were described in Materials and Methods.