TABLE 6

Clinically observed and PBPK model-predicted pharmacokinetic parameters of bosutinib in subjects with hepatic impairment after a single oral administration of 200 mg bosutinib

Data are expressed as geometric means with percent coefficients of variation in parentheses or as median t_max values with ranges in parentheses.

Population	Analysis	PK Parameter				Ratio^{^b}
Population	Analysis	F_a^{^a}	C_max	t_max	AUC	C_maxR	AUCR
			ng/ml	h	ng⋅h/ml
HVs	Observed	―	32 (31)	4.0 (1.0–8.0)	714 (43)	―	―
	Predicted	0.50	29 (43)	3.4 (2.6–4.7)	752 (53)	―	―
	P/O	―	0.9	―	1.1	―	―
HIPs
Child–Pugh A	Observed	―	78 (52)	2.5 (0.5–4.0)	1720 (26)	2.4	2.4
	Predicted	0.50	39 (44)	2.0 (1.6–2.7)	1265 (59)	1.4	1.7
	P/O	―	0.5	―	0.7	0.6	0.7
	Predicted	0.68	53 (42)	2.0 (1.6–2.7)	1710 (58)	1.8	2.3
	P/O	―	0.7	―	1.0	0.8	1.0
Child–Pugh B	Observed	―	64 (35)	2.0 (1.0–4.0)	1350 (40)	2.0	1.9
	Predicted	0.50	48 (38)	2.1 (1.6–2.9)	1942 (50)	1.7	2.6
	P/O	―	0.8	―	1.4	0.8	1.4
	Predicted	0.35	34 (38)	2.1 (1.6–2.9)	1359 (50)	1.2	1.8
	P/O	―	0.5	―	1.0	0.6	1.0
Child–Pugh C	Observed	―	49 (70)	1.5 (1.0–3.0)	1270 (47)	1.5	1.8
	Predicted	0.50	59 (34)	2.0 (1.6–2.7)	2734 (43)	2.1	3.6
	P/O	―	1.2	―	2.2	1.4	2.0
	Predicted	0.23	27 (34)	2.0 (1.6–2.7)	1257 (43)	0.9	1.7
	P/O	―	0.6	―	1.0	0.6	0.9

Dashes indicate not applicable.
↵^a Predicted F_a was first fixed at 0.5 and then calculated from the simulation results with F_a of 0.5.
↵^b Ratios of C_max and AUC in HIPs to HVs.