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 CLint,T Value	Simulated Digoxin CLR
	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 CLRa (Population representative using trial design 1 mg, i.v. bolus (Kramer et al., 1979))	4.14	133.4
Overall weighted mean CLRa (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.

^aCL_R data presented in Supplemental Table S4.