TABLE 4

IVIVE of metformin CL_h,s,in based on the REF approach

	HEK293	PHH
	HEK293	ADR	FEA	JEL	YTW	Average ± S.D.
(μl/min per milligram protein)	8.05 ± 0.64	0.81 ± 0.06	0.60 ± 0.05	0.65 ± 0.45	0.45 ± 0.08	0.63 ± 0.15
(μl/min per milligram protein)	0.22 ± 0.06	0.07 ± 0.06	0.04 ± 0.02	0.15 ± 0.07	0.1 ± 0.06	0.09 ± 0.05
In vitro total OCT1 protein abundance (pmol/mg protein)	17.34 ± 0.35	3.21 ± 0.12^{^a}	1.92 ± 0.33^{^a}	1.04 ± 0.06^{^a}	0.71 ± 0.04^{^a}	1.72 ± 1.12
Ex vivo hepatic tissue OCT1 protein abundance (pmol/mg protein)^{^b}	4.68 ± 1.9
Scaling factor: [E]_ex _vivo/[E]_{in vitro}	0.27	1.46	2.43	4.5	6.59	3.75 ± 2.28
Protein yield MGMPGL (mg total membrane protein/g of liver)^{^b}	37.68
Protein yield MGPGL (mg total protein/g of liver)^{^c}	120
IVIVE CL_h,s,in assuming 100% plasma membrane abundance (ml/min) (eqs. 6–8)	224 ± 81	116 ± 44	139 ± 55	285 ± 109	284 ± 111	168 ± 64
IVIVE CL_h,s,in based on the WSHM and assuming 100% plasma membrane abundance (ml/min) (eq. 5)	192 ± 62	107 ± 38	126 ± 46	235 ± 78	234 ± 79	149 ± 52
%PMA	36 ± 2.5	64 ± 9.3^{^a}	55 ± 6.4^{^a}	52 ± 11.5^{^a}	66 ± 4.2^{^a}	59 ± 6.7
IVIVE CL_h,s,in (ml/min) corrected for OCT1 PMA (eq. 6)	578 ± 225	178 ± 69	248 ± 99	535 ± 210	425 ± 169	277 ± 109
IVIVE CL_h,s,in (ml/min) based on the WSHM and corrected for OCT1 PMA (eq. 5)	405 ± 122	157 ± 56	208 ± 74	382 ± 119	323 ± 105	230 ± 78

↵^a OCT1 abundance and %PMA were obtained from our previous report (Kumar et al., 2019).
↵^b Each hepatic tissue (n = 36) OCT1 total abundance and the corresponding protein yield MGMPGL were obtained from our previous report (Wang et al., 2016).
↵^c Value for the yield of total milligrams of protein per gram of liver was obtained based on hypocellularity and total protein per million hepatocytes (Jones et al., 2012; Kim et al., 2019).