TABLE 7

PBPK model–predicted pharmacokinetic parameters of crizotinib in healthy subjects following 28-day multiple oral administration of crizotinib with and without coadministration of a weak or moderate CYP3A inhibitor

Data are expressed as geometric mean with percent coefficient of variation (CV%) in parentheses (n = 15 per group × 6 groups). Dose levels were crizotinib 150 mg twice daily with diltiazem 120 mg twice a day, erythromycin 500 mg three times a day, fluconazole 200 mg once a day, or fluvoxamine 50 mg once a day.

	Control Group^{^a}		Treatment Group		Fold Increase^{^b}
CYP3A Inhibitor	C_max	AUC_0–_τ	C_max	AUC_0–_τ	C_maxR	AUC_R
	ng/ml	ng⋅h/ml	ng/ml	ng⋅h/ml	ratio	ratio
	114 (57)	1359 (57)
Diltiazem			123 (56)	1476 (57)	1.1 (6.2)	1.1 (6.2)
Erythromycin			179 (44)	2141 (44)	1.6 (26)	1.6 (26)
Fluconazole			199 (48)	2378 (48)	1.8 (26)	1.8 (26)
Fluvoxamine			114 (56)	1368 (57)	1.0 (0.6)	1.0 (0.6)

↵^a Mean values in the control groups of these simulation results.
↵^b Fold increase in C_max and AUC_0–∞ of the treatment group (crizotinib with CYP3A inhibitor) relative to control group (crizotinib alone).