TABLE 4

Pharmacokinetic parameters for nine CYP3A substrates after 2 mg/kg oral administration of each CYP3A substrate with a concomitant oral dose of vehicle or 5 mg/kg ketoconazole in cynomolgus monkeys

Each value represents the mean ± S.D. of four monkeys.

	C_max	T_max	t_1/2	AUC_inf
	ng/ml	h	h	h · ng/ml
Buspirone
+ Vehicle	0.51 ± 0.42	1.0 ± 0.0	1.43 ± 0.35	1.18 ± 0.86
+ Ketoconazole	8.52 ± 4.84^*	1.3 ± 0.5	1.15 ± 0.41	15.15 ± 4.67^*
Carbamazepine
+ Vehicle	761 ± 214	1.1 ± 0.3	2.57 ± 0.17	2367 ± 1442
+ Ketoconazole	663 ± 235	1.0 ± 0.0	2.49 ± 0.29	2351 ± 1787
Diazepam
+ Vehicle	30.4 ± 14.9	1.3 ± 0.5	3.37 ± 1.49	90.6 ± 43.6
+ Ketoconazole	39.3 ± 42.7	2.1 ± 2.6	3.32 ± 1.10	156 ± 149
Felodipine
+ Vehicle	0.92 ± 0.38	3.5 ± 1.0	7.68 ± 3.81	12.2 ± 7.30
+ Ketoconazole	6.09 ± 5.33	1.5 ± 0.6	5.30 ± 2.16	32.7 ± 20.6
Midazolam
+ Vehicle	37.4 ± 16.3	2.0 ± 0.0	2.50 ± 1.65	221 ± 145
+ Ketoconazole	255 ± 311	3.3 ± 3.2	2.96 ± 0.69	1332 ± 1321
Nicardipine
+ Vehicle	67.3 ± 15.7	1.0 ± 0.0	6.17 ± 2.54	144 ± 36.4
+ Ketoconazole	150 ± 52.1^*	1.8 ± 0.5	3.91 ± 0.71	443 ± 52.7^*
Nifedipine
+ Vehicle	9.22 ± 2.50	2.5 ± 2.4	3.91 ± 3.28	43.2 ± 23.4
+ Ketoconazole	75.6 ± 40.8^*	1.3 ± 0.5	2.02 ± 1.66	146 ± 47.8^*
Saquinavir
+ Vehicle	2.49 ± 0.86	1.1 ± 0.6	9.40 ± 13.0	7.45 ± 4.91
+ Ketoconazole	36.9 ± 19.5^*	0.8 ± 0.3	7.59 ± 1.65	66.7 ± 23.5^*
Verapamil
+ Vehicle	1.88 ± 1.32	1.5 ± 0.6	3.22 ± 1.40	10.4 ± 11.4
+ Ketoconazole	12.2 ± 11.6	1.5 ± 0.6	4.28 ± 2.48	55.5 ± 51.6

↵* p < 0.05, compared with vehicle.