TABLE 2

The in vitro to in vivo scaling factors estimated for literature compounds

Compound	In vivo fitted parameters		Serum free buffer in vitro scaled-up parameters^d				10% human or monkey serum buffer In vitro scaled-up parameters^d
Compound	CL_{u,int,passive}	CL_u,int,active	CL_{u,int,passive}	CL_u,int,active	SF1^e CL_{u,int,passive}	SF1^e CL_u,int,active	CL_{u,int,passive}	CL_u,int,active	SF2^e CL_{u,int,passive}	SF2^eCL_u,int,active
Human
Bosentan^a	59	8489	65.6	315.9	0.9	26.9	36.1	1180.8	1.6	7.2
Cerivastatin^a	153	12,827	71.0	697.5	2.2	18.4	135.2	2855.6	1.1	4.5
Fluvastatin^a	147	76,513	64.3	721.6	2.3	106.0	301.2	3225.0	0.5	23.7
Pitavastatin^c	52.6	16,071.3	66.9	603.8	0.8	26.6	174.0	3989.5	0.3	4.0
Pravastatin^a	4.2	406	8.0	22.8	0.5	17.8	8.0	38.8	0.5	10.5
Repaglinide^a	1477	13,941	191.4	642.6	7.7	21.7	143.2	3308.1	10.3	4.2
Rosuvastatin^a	1.7	1190	18.7	162.0	0.1	7.3	17.4	250.3	0.1	4.8
Valsartan^a	23	2463	30.8	69.6	0.7	35.4	354.8	1063.0	0.1	2.3
Median					0.8	24.2			0.5	4.6
Monkey
Bosentan^b	2.1	595.8	0.4	7.8	4.7	76.8	0.7	54.9	2.8	10.8
Pitavastatin^c	0.2	405.7	0.5	17.9	0.4	22.7	1.2	89.5	0.2	4.5
Rosuvastatin^b	0.2	52.2	0.2	4.8	0.9	10.9	0.2	7.3	0.6	7.1
Median					0.9	22.7			0.6	7.1

↵^a In vivo fitted intrinsic clearance in human (except for pitavastatin) was reported previously (Jones et al., 2012).
↵^b In vivo fitted intrinsic clearance (bosentan and rosuvastatin) in monkey were from Morse et al. (2017).
↵^c In vivo fitted intrinsic clearance of Pitavastatin in human and monkey was modeled in house.
↵^d In vitro scaled intrinsic clearance was calculated by in vitro uptake clearance × hepatocellularity × liver weigh per body weight. Human is assumed to have 70 kg body weight.
↵^e SF1 = in vivo fitted value/in vitro scaled value in serum free buffer; SF2 = in vivo fitted value/in vitro scaled value in 10% serum buffer.