TABLE 1

Nonspecific binding of validation set drugs and TKIs to HLM (0.25 mg/ml)

Drug	fu_mic ± S.D. + CHAPS (6 mM)	fu_mic ± S.D. − CHAPS	Ionized at pH 7.4	Log P	Predicted fu_mic by SimCYP	Predicted fu_mic by Austin et al. (2002)^{^a}	Predicted fu_mic by Hallifax and Houston (2006)^{^b}
			%
Validation set drugs
Amitriptyline	0.91 ± 0.03	0.64 ± 0.07	99	4.81^{^c}–5.10^{^d}	0.26–0.35	0.13–0.17	0.25–0.35
Chlorpromazine	0.72 ± 0.05	0.36 ± 0.06	98	4.54^{^c}–5.20^{^e}	0.26–0.45	0.11–0.23	0.21–0.47
Felodipine	0.26 ± 0.02	0.25 ± 0.06	1	3.44^{^c}–4.83^{^e}	0.39–0.77	0.17–0.55	0.35–0.82
Isradipine	0.75 ± 0.02	0.72 ± 0.04	0	2.00^{^c}–4.30^{^f}	0.55–0.95	0.29–0.89	0.56–0.95
Loratidine	0.47 ± 0.05	0.44 ± 0.06	1	4.21^{^d}–5.94^{^c}	0.15–0.56	0.05–0.31	0.06–0.60
Midazolam	0.83 ± 0.03	0.86 ± 0.06	13	2.50^{^f}–3.97^{^c}	0.64–0.91	0.38–0.80	0.68–0.93
Nifedipine	0.88 ± 0.03	0.87 ± 0.02	1	1.82^{^c}–2.97^{^e}	0.85–0.96	0.69–0.91	0.89–0.96
Pazopanib	0.73 ± 0.03	0.75 ± 0.03	1	1.98^{^e}–3.59^{^d}	0.74–0.95	0.50–0.89	0.78–0.95
Zidovudine	1.00 ± 0.02	1.01 ± 0.04	100	0.53^{^e}–1.16^{^c}	0.98–0.99	0.96–0.98	0.97–0.98
TKIs
Axitinib	0.79 ± 0.03		0.2	4.15^{^c}–4.20^{^f}	0.58–0.59	0.31–0.33	0.60–0.62
Dabrafenib	0.81 ± 0.06	0.79 ± 0.02	64	3.54^{^e}–5.46^{^c}	0.33–0.75	0.08–0.52	0.14–0.79
Erlotinib	0.92 ± 0.02	0.89 ± 0.03	1	2.39^{^e}–3.30^{^f}	0.80–0.92	0.59–0.83	0.84–0.93
Gefitinib	0.76 ± 0.05		22	3.75^{^c}–4.11^{^e}	0.70–0.60	0.34–0.45	0.63–0.74
Ibrutinib	0.57 ± 0.04		13	2.76^{^d}–3.63^{^c}	0.73–0.89	0.49–0.75	0.77–0.91
Lapatinib	0.25 ± 0.02		31	4.64^{^c}–5.18^{^d}	0.30–0.45	0.11–0.21	0.22–0.42
Nintedanib	0.93 ± 0.03		59	2.59^{^e}–3.70^{^d}	0.72–0.91	0.47–0.78	0.76–0.92
Nilotinib	0.43 ± 0.04		7	4.51^{^d}–5.36^{^c}	0.25–0.49	0.09–0.23	0.17–0.48
Regorafenib	0.14 ± 0.03		0.1	4.20^{^f}–5.26^{^e}	0.27–0.58	0.10–0.31	0.19–0.60
Sorafenib	0.14 ± 0.03		0.1	4.20^{^f}–5.16^{^e}	0.30–0.58	0.12–0.31	0.23–0.60
Trametinib	0.58 ± 0.02		0	2.68^{^e}–3.45^{^d}	0.77–0.89	0.55–0.76	0.81–0.91

↵^a Predicted values calculated using the equation fu_inc = 1/C · 10^{0.56 log P − 1.41} + 1.
↵^b Predicted values calculated using the equation fu_inc = 1/1 + C · 10^{0.072(log P)2 + 0.067 ⋅ log P − 1.126}.
↵^c Marvin.
↵^d ALOGPS2.1.
↵^e ACD/Laboratories.
↵^f XlogP3.