TABLE 2

Values of the OATP4C1 CL_int,T parameter estimated by various methods and subsequent simulated digoxin CLR in healthy volunteers using the intravenous trial design from Greiner et al. (1999)

Source of Data	OATP4C1 CL_int,T Value	Simulated Digoxin CL_R
	µl/min/million PTC	ml/min
In vitro–in vivo extrapolation
MDCK-OATP4C1 (Mikkaichi et al., 2004)	0.23	90.6
CHO-OATP4C1 (Chu et al., 2007)	270	804.3
Parameter estimation: Fitting to plasma concentration-time profile
1 mg, i.v. bolus (n = 12 subjects) (Kramer et al., 1979)	8.20
0.01 mg/kg, i.v. 4 min infusion (n = 12 subjects) (Rengelshausen et al., 2003)	1.10
0.5 mg, i.v. 5 min infusion (n = 12 subjects) (Ding et al., 2004)	0
0.75 mg, i.v. bolus (n = 8 subjects) (Koup et al., 1975)	0.09
0.75 mg, i.v. 1 h infusion (n = 8 subjects) (Koup et al., 1975)	5.56
0.75 mg, i.v. 3 min infusion (n = 8 subjects) (Johnson and Bye, 1975)	3.30
0.5 mg, i.v. 1 h infusion (n = 9 subjects) (Ochs et al., 1978)	0
1 mg, i.v. 1 h infusion (n = 9 subjects) (Ochs et al., 1978)	0
1.5 mg, i.v. 1 h infusion (n = 9 subjects) (Ochs et al., 1978)	0
Overall weighted mean ± standard deviation	1.85 ± 2.87	108.8
Parameter estimation: Sensitivity analysis
Overall weighted mean CL_R^{^a} (Population representative using trial design 1 mg, i.v. bolus (Kramer et al., 1979))	4.14	133.4
Overall weighted mean CL_R^{^a} (Population representative using trial design 0.01 mg/ kg, i.v. 4 min infusion (Rengelshausen et al., 2003))	4.14	133.4

PTC, proximal tubule cells; MDCK, Madin-Darby canine kidney.
↵^a CL_R data presented in Supplemental Table S4.