TABLE 5

Pharmacokinetic parameters, fraction of drug escaping intestinal metabolism (f_g) derived from human in vitro systems using the model of competing rates (Eq. 7) and f_g derived from in vivo pharmacokinetic profiles of rat and human

Compound	Oral Bioavailability in Humans^{^a}	Human f_a (PBPK)	Human CL^{^a}	Human f_g Derived from In Vivo Pharmacokinetic Profiles				Human f_g Derived from Human In Vitro Systems			Rat f_g PBPK
Compound	Oral Bioavailability in Humans^{^a}	Human f_a (PBPK)	Human CL^{^a}	Indirect Method^{^b}^,^{^c}	GFJ^{^d}	PBPK	HIM^{^e}	S9	rCYP	HLM	Rat f_g PBPK
	F		ml/min per kg
Alprazolam	0.92	1	0.8	0.96	0.89	0.94	0.99	0.98	0.86	1.00	1.00
Atorvastatin	NA	NA	NA	NA	0.56	NA	0.90	1.00	NA	NA	0.16
Buspirone	0.04	1	17	0.21	0.11	0.12	0.68	0.64	0.18	0.47	0.10
Cyclosporine A	0.22	0.8	5.9	0.31	0.65	0.6	0.82	0.46	0.26	0.53	0.48
Erythromycin	0.16	0.95	4.9	0.21	NA	0.23	NA	0.57	0.74	0.87	NA
Felodipine	0.19	1	10.5	0.38	0.53	0.38	0.20	0.44	0.07	0.52	NA
Indinavir	NA	NA	NA	NA	1	NA	0.25	0.18	NA	NA	0.80
Midazolam	0.42	1	6.1	0.59	0.57	0.52	0.54	0.44	0.29	0.40	0.85
Nifedipine	0.4	1	4.64	0.51	0.62	0.47	0.66	0.36	0.05	0.28	0.67
Paracetamol	0.62	1	5.2	0.82	NA	0.86	NA	1.00	NA	NA	1.00
Saquinavir	0.002	0.020	14.5	0.0065	0.54	0.47	0.01	0.01	NA	NA	NA
Sildenafil	0.42	0.92	8.1	0.68	0.82	0.7	0.78	0.44	0.29	0.46	0.41
Tacrolimus	0.3	1	0.8	0.31	NA	0.36	0.34	0.15	0.08	0.12	0.25
Terfenadine	NA	NA	NA	NA	0.4	0.4	0.11	0.54	NA	0.46	NA
Triazolam	0.56	1	2.2	0.63	0.4	0.63	0.95	0.91	0.79	0.88	NA
Verapamil	0.22	1	10.8	0.45	0.71	0.42	0.67	0.78	0.46	0.74	0.62

GFJ, grapefruit juice-drug interaction studies; NA, not available; rCYP, recombinant CYP3A4.
↵^a Pharmacokinetic parameters are derived by applying noncompartmental analysis to the PBPK-simulated i.v. profile that best fits the observed.
↵^b For the indirect method, the fraction absorbed is assumed 1.
↵^c Data are from Galetin et al., 2008.
↵^d Data are from Gertz et al., 2008.
↵^e Data are from Gertz et al., 2010.