TABLE 2.

Pharmacokinetics of a single dose of bosutinib 100 and 200 mg and multiple doses (100 mg once daily) for 3 months in plasma and cerebrospinal fluid (CSF) and the corresponding predicted values in plasma and CSF

		Expected/observed			Expected/observed	Predicted	Predicted	Predicted	Predicted
	Patients (n)	9	9	Subjects [n]	6	6	6	6	6
Single oral dose		100 mg	200 mg		500 mg	400 mg	300 mg	200mg	100mg
Plasma	Cmax (ng/mL)	13.5 ± 15.1	19.6 ± 12.1	Cmax (ng/mL)	87.9 ± 30.8	70.3 ± 24.6	52.7 ± 18.5	35.2 ± 12.3	17.6 ± 6.16
	Cmax (nM)	25.5 ± 28.5	37 ± 14.5
	Tmax (hrs)	3	4	Tmax (hrs)	3.50 (2.00–6.00)	3.50 (2.00–6.00)	3.50 (2.00–6.00)	3.50 (2.00‐6.00)	3.50 (2.00‐6.00)
	AUC0‐4 (ng/mL*hr)	25.4 ± 11.8	36.9 ± 2.81
	AUC0‐4 (nM*hr)	47.9 ± 22.3	69.6 ± 5.3	AUC0‐24 [ng/h/mL]	2190 ± 661	1752 ± 529	1314 ± 397	876 ± 264	438 ± 132
CSF	Cmax (ng/mL)	0.06 ± 0.04	0.13 ± 0.06	t ½ [h]	39.70 ± 8.49	31.8 ± 6.8	23.8 ± 5.09	15.9 ± 3.4	7.94 ± 1.7
	Cmax (nM)	0.11 ± 0.08	0.25 ± 0.09
	Tmax (hrs)	2	4
	AUC0‐4 (ng/mL*hr)	0.14 ± 0.04	0.24 ± 0.03
	AUC0‐4 (nM*hr)	0.26 ± 0.07	0.44 ± 0.06

		Expected/observed	Predicted	Predicted	Predicted	Predicted
	Patients (n)	13	13	13	13	13
Multiple oral doses		100 mg	200 mg	300 mg	400 mg	500 mg
Plasma	Cmax (ng/mL)	29.93 ± 10.27	59.9 ± 20.5	89.8 ± 30.8	120 ± 41.1	150 ± 51.4
	Cmax (nM)	56.43 ± 19.34	113 ± 38.7	169 ± 58	226 ± 77.4	282 ± 96.7
	Tmax (hrs)	4	4	4	4	4
	AUC0‐4 (ng/mL*hr)	73.1 ± 6.63	146 ± 13.3	219 ± 19.9	292 ± 26.5	366 ± 33.2
	AUC0‐4 (nM*hr)	137.8 ± 12.5	276 ± 25	413 ± 37.5	551 ± 50	689 ± 62.5
CSF	Cmax (ng/mL)	0.5 ± 0.17	1.0 ± 0.45	1.5 ± 0.52	2.0 ± 0.69	2.5 ± 0.86
	Cmax (nM)	0.94 ± 0.32	1.9 ± 0.64	2.82 ± 0.96	3.76 ± 0.1.28	4.7 ± 1.6
	Tmax (hrs)	3	3	3	3	3
	AUC0‐4 (ng/mL*hr)	1.15 ± 0.15	2.3 ± 0.59	3.45 ± 0.47	4.6 ± 0.63	5.75 ± 0.79
	AUC0‐4 (nM*hr)	2.16 ± 0.21	4.32 ± 0.59	6.48 ± 0.89	8.64 ± 1.18	10.8 ± 1.49

Notes: AUC_0‐4: area under the curve at 0 to 4 hours; T_max: maximum time; C_max: maximum concentration, T_1/2: elimination.