Table III.

Summary of Observed and Predicted Food Effects (Represented as Fold Difference) for Seven Novartis Compounds with Respect to Area Under the Plasma Concentration–Time Curve (AUC_0−last) and Peak Plasma Concentration (C _max)

Compound	Modeling approacha	Dose (mg)	Formulations	Human C max ratio (fed/fasted)			Human AUC0−last ratio (fed/fasted)			Dog observed AUC (C max) Ratio (fed/fasted)
				Predicted	Observed	Prediction fold error	Predicted	Observed	Prediction fold error
NVS732	Prospective	100	Tablet	0.84	0.90	1.07	0.99	0.88	1.12
NVS406	Prospective	150	Suspension	4.84	6.11	1.26	3.98	4.35	1.09	Suspension: 5.57 (4.62)d; liquid form: 1.30 (0.99)d
NVS406	Prospective	450	Suspension	7.54	6.12	1.23	6.86	4.34	1.58
NVS562	Pro./Retro.	50	SEDDS	0.82b, 0.88c	0.85	1.04b, 1.04c	0.97b, 0,94c	1.01	1.04b, 1.08c
NVS562	Pro./Retro.	50	Tablet, salt	1.48b, 1.77c	1.60	1.08b, 1.11c	1.57b, 1.70c	1.59	1.01b, 1.07c
NVS701	Prospective	200	Capsule F1	1.57	1.71	1.09	1.71	1.55	1.10	2.04 (1.73)d
NVS701	Prospective	200	Capsule F2	1.37	1.37	1.00	1.42	1.35	1.05	1.53 (1.39)d
NVS001	Retrospective	300	Tablet	0.28	0.28	1.00	0.27	0.31	1.15	0.14 (0.08)e
NVS169	Prospective	100	ME	0.96	0.52	1.84	1.14	1.01	1.13
NVS113	Prospective	30	SF	0.93	0.60	1.53	0.97	0.71	1.37	1.09 (1.03)d

^aProspective prediction and/or retrospective analysis are done to analyze the human food effects. In this study, if the parameters used in the models are not optimized using observed human PK data in the food effect study, the modeling approach is considered as prospective prediction. Retrospective analysis can be used to refine the model if parameters in the model are unknown or can not be well characterized from experiments

^bPredicted with the mean precipitation time fitted against the in vivo plasma concentration–time curve

^cPredicted with the mean precipitation time using in vitro dissolution/precipitation test

^dResults obtained from dog studies

^eResults obtained from primate studies