Table 2.

Prediction of the potential DDI risks in vivo based on the AUC ratios.

Inhibitor	Enzyme source	Eha	fhepb	Ki,uc	Cmax,ud	AUC ratiose	AUC increased
				(μmol/L)	(μmol/L)		(%)
Icotinib	HLM	0.1–0.9	1	8.55	0.53	1.01–1.06	1%–6%
Erlotinib	HLM	0.1–0.9	1	1.23	0.55	1.05–1.43	5%–43%

^aE_h is the hepatic extraction ratio ranging from 0.1 to 0.9 for UGT1A1 substrates.

^bThe f_hep was set to 1.

^cThe K_i,u values of erlotinib and icotinib is the same to the K_i values, due to the negligible binding of erlotinib or icotinib to HLMs (0.2 mg/mL).

^dThe C_max of icotinib in humans was 4.79 μmol/L after a 125 mg × 3 daily dose of icotinib hydrochloride; The C_max of erlotinib in humans was 6.06 μmol/L after a single 150 mg dose of erlotinib. The unbound C_max of erlotinib or icotinib (C_max,u) were calculated as C_max × f_u (f_u was determined as 0.09 and 0.11 for erlotinib and icotinib, respectively).

^ePrediction methods as described in the materials and method.