Table 1.

Regression analysis of various P450 isoform-selective marker activities with astemizole metabolism in a panel of human liver microsomes.

		Correlation coefficient (r)
Reaction	P450 isoform	DES-AST formationa	NOR-AST formationb	6OH-AST formationca
7-Ethoxyresorufin O-dealkylation	CYP1A2	0.067	0.199	0.202
Coumarin 7-hydroxylation	CYP2A6	0.169	0.545	0.025
7-Ethoxy-4-trifluoromethylcoumarin deethylation	CYP2B6	0.215	0.496	0.273
Taxol 6-hydroxylation	CYP2C8	0.241	0.207	0.293
Tolbutamide hydroxylation	CYP2C9	0.183	−0.091	0.025
S-Mephenytoin 4′-hydroxylation	CYP2C19	0.291	0.225	−0.149
Dextromethorphan O-demethylation	CYP2D6	0.086	0.275	−0.039
Chlorozoxazone 6-hydroxylation	CYP2E1	0.130	−0.190	0.450
Testosterone 6β-hydroxylation	CYP3A4/5	0.470	0.577	0.884**
Dextromethorphan N-demethylation	CYP3A4	0.459	0.785*	0.756**
Lauric acid 12-hydroxylation	CYP4A11	−0.013	−0.321	−0.113

a) Correlation coefficient was determined with the liver tissue of 15 different organ donor subjects, except for correlation involving 7-ethoxy-4-trifluoromethylcoumarin deethylation (n = 14). b) Correlation coefficient was determined with the liver tissue of seven different organ donor subjects. The statistical significance of the correlation is denoted by

^*P < 0.05

^**P < 0.01. Astemizole (1 µm) was incubated with human liver microsomes (0.1 mg ml⁻¹) and an NADPH-generating system for 20 min at 37°C.