TABLE 8

PBPK model-predicted pharmacokinetic parameters of bosutinib in patients with renal and hepatic impairment after multiple 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 (n = 10 per group × 10 groups).

Study	Population	PK Parameter				Ratio^{^b}
Study	Population	F_a^{^a}	C_max	t_max	AUC	C_maxR	AUCR
			ng/ml	h	ng⋅h/ml
RIPs	HVs	0.60	57 (51)	4.4 (3.0–6.2)	1029 (57)	―	―
	Moderate RIPs	0.60	95 (57)	4.9 (3.6–7.0)	1861 (62)	1.7	1.8
	Severe RIPs	0.60	98 (57)	5.0 (3.8–6.8)	1941 (62)	1.7	1.9
HIPs	HVs	0.50	52 (49)	3.4 (2.6–4.6)	854 (56)	―	―
	Child–Pugh A	0.68	120 (60)	2.8 (2.0–4.0)	2117 (70)	2.3	2.5
	Child–Pugh B	0.35	97 (57)	2.8 (2.0–4.0)	1870 (64)	1.9	2.2
	Child–Pugh C	0.23	94 (51)	2.6 (2.0–4.0)	1899 (56)	1.8	2.2

Dashes indicate not applicable.
↵^a Predicted F_a was fixed at the values used for the single-dose simulation.
↵^b Ratios of C_max and AUC in RIPs or HIPs to HVs.