TABLE 4

The partition coefficients and free partition coefficients of brain for EGFR inhibitors

	AEE788	Afatinib	AZD3759	Dacomitinib	Erlotinib	Gefitinib	Osimertinib	Vandetanib
K_p,brain, wild type	0.066	0.254	1.70	0.612	0.062	0.358	0.988	0.635
K_p,brain, TKO	1.86	2.41	2.65	9.77	0.204	2.20	15.7	7.47
f_u,p	0.068	0.080	0.058	0.008	0.045	0.041	0.005	0.055
f_u,b	0.029	0.014	0.101	0.007	0.096	0.012	0.001	0.012
K_p,uu, wild-type	0.029	0.046	2.96	0.493	0.134	0.103	0.289	0.138
K_p,uu, TKO	0.804	0.433	4.61	7.88	0.438	0.631	4.61	2.65
DA	28.1	9.49	1.56	16.0	3.27	6.16	15.9	19.1

DA, distribution advantage calculated by the ratios of K_p,brain in transgenic to K_p,brain in wild type; f_u,b, free fraction in brain homogenate measured by rapid equilibrium dialysis (n = 4); f_u,p, free fraction in plasma measured by rapid equilibrium dialysis (n = 4); K_p, the ratio of AUC_{last, brain} to AUC_{last, plasma} using total drug concentrations; K_p,uu, the ratio of AUC_{last, brain} to AUC_{last, plasma} using free drug concentrations.