Table 2.

Exposure of regorafenib in plasma, eye, and BoE, based on regimens used in animal and human studies

		Unbound fraction	Dose a (mg day –1 )	AUC(0–24) (μg h l –1 )	AUC u(0–24) b (μg h l –1 )
Rat topical 14	Plasma	0.0072	0.4	222	1.6
	Eye		0.4	15 100	109
Monkey topical c [data on file]	Plasma	0.022	1d	108	2.38
13	BoE		2	1362	30.0
Human topical (from DREAM study)	Plasma	0.005	2.25	76	0.38
	BoE (estimated)		2.25	963	4.82
Human oral 17	Plasma	0.005	160	58 300	292
	Plasma		10	5670	28.5

All data except the human topical data are from sources other than the presented phase IIa (DREAM) study. Data sources are indicated by reference numbers. AUC(0–24), area under the curve from time 0 to 24 h; AUC_u, area under unbound concentration curve; BoE, back of the eye; DREAM, Developing Regorafenib Eye drops for neovascular Age‐related Macular degeneration

^aDose per eye in case of topical applications

^bUnbound AUC

^cAUC values were calculated from dose‐normalized data and then multiplied with dose per eye

^dBoth eyes treated, 1 mg per eye. A total dose of 2 mg is therefore comparable to results for exposure in eye