TABLE 1

Bioavailability and intestinal availability for CYP3A and P-gp substrates

Compound	Dose_iv	Dose_po	R_b	F	F_h^{^a}	Observed F_aF_g	Reference
	mg	mg
Felodipine	2.5	2.5	0.7	0.152	0.377	0.240^{^b}	Edgar et al., 1985; Uchimura et al., 2010^{^c};
Midazolam	2	6	0.824	0.253	0.638	0.396	Tsunoda et al., 1999; Perdaems et al., 2010
Sildenafil	50	50	0.64	0.41	0.548	0.748	(ichols et al., 2002; Gertz et al., 2010
Triazolam	0.25	0.25	0.760	0.44	0.866	0.508	Vanderveen et al., 1991; Kroboth et al., 1995
Celiprolol	20	100	0.870^{^d}	0.296	0.851	0.348	Caruso et al., 1985
Digoxin	0.01 (mg/kg)	0.75	0.96	0.553	0.899	0.615	Rengelshausen et al., 2003; Uchimura et al., 2010
Fexofenadine	0.1	0.1	0.74	0.410	0.890	0.461	Lappin et al., 2010
Talinolol	30	100	0.941^{^d}	0.453	0.924	0.490	Wetterich et al., 1996
Indinavir	16^{^e}	400	0.84	0.6	0.521	1.15	Yeh et al., 1998, 1999; Gertz et al., 2010
Quinidine	400^{^f}	0.1^{^g}	0.919	0.160	0.848	0.189	Hughes et al., 1975; Ueda et al., 1976; Maeda et al., 2011
Quinidine	400^{^f}	1^{^g}	0.919	0.207	0.848	0.245	Hughes et al., 1975; Ueda et al., 1976; Maeda et al., 2011
Saquinavir	12	600	0.74	0.007	0.317	0.0221	Kupferschmidt et al., 1998; Gertz et al., 2010^{^h};
Verapamil	10	0.1^ⁱ	0.885	0.0677	0.482	0.140	Fromm et al., 1996; Maeda et al., 2011
Verapamil	10	3^ⁱ	0.885	0.0802	0.482	0.166	Fromm et al., 1996; Maeda et al., 2011

↵^a F_h was calculated using a hepatic blood flow rate of 25.5 ml/min/kg (Wynne et al., 1989), except for felodipine.
↵^b F_h for felodipine was calculated using a hepatic blood flow rate of 43.4 ml/min/kg (Bengtsson-Hasselgren et al., 1990).
↵^c Interview form of felodipine (Splendil), AstraZeneca K.K. (Osaka, Japan).
↵^d Calculated based on an in silico prediction method (Uchimura et al., 2010).
↵^e i.v.-Administered stable isotope compound was taken with 400 mg of unlabeled compound orally.
↵^f Dose of quinidine gluconate, including 58.3% of quinidine.
↵^g Dose of quinidine sulfate, including 82.9% of quinidine.
↵^h Interview form of saquinavir (Invirase), Chugai Pharmaceutical Co., Ltd. (Tokyo, Japan).
↵ⁱ Dose of verapamil hydrochloride, including 92.6% of verapamil.