TABLE 4

Predicted and observed AUC changes of NGMN determined retrospectively from clinical trials

The perpetrator in vitro values shown in Table 3 were used for the DDI predictions. Equations 2–4, as defined in Materials and Methods, were used to calculate the fold changes in the AUC. LPR and RTV were coadministered in one study (Vogler et al., 2010), while ATV and RTV were coadministered in another study (Zhang et al., 2011). Hence, the fold AUC changes are the same for LPR and RTV (study 1) and ATV and RTV (study 2). EFZ was dosed in a separate study (Sevinsky et al., 2011).

Perpetrator			NGMN		Predicted/Observed Ratio
Concentration Paradigm	Dose	Concentration	Predicted AUC_i/AUC	Observed AUC_i/AUC	Predicted/Observed Ratio
	mg	nM
Total C_max	LPR (400)	14,790	2.3	1.82	1.28
Free C_max	LPR (400)	118	2.2	1.82	1.24
I_h	LPR (400)	42,526	2.3	1.82	1.28
Total C_max	RTV study 1 (100)	745	2.3	1.82	1.28
Free C_max	RTV study 1 (100)	2	2.1	1.82	1.17
I_h	RTV study 1 (100)	9249	2.3	1.82	1.28
Total C_max	ATV (300)	9616	2.3	1.83	1.27
Free C_max	ATV (300)	1298	2.3	1.83	1.26
I_h	ATV (300)	29,667	2.3	1.83	1.27
Total C_max	RTV study 2 (100)	2053	2.3	1.83	1.27
Free C_max	RTV study 2 (100)	6	2.3	1.83	1.27
I_h	RTV study 2 (100)	9253	2.3	1.83	1.27
Total C_max	EFZ (600)	21,161	0.4	0.36	0.98
Free C_max	EFZ (600)	127	0.9	0.36	2.49
I_h	EFZ (600)	126,842	0.7	0.36	1.94