Values used for IVIVE of metformin CLr,sec

Human in vivo CLr,sec of metformin: geometric mean (range) 415 (215–643) ml/minHEK293MDCKII
Human kidney weight (g)150150
Cortex weight/kidney (70% of total kidney weight) (g)a105105
OCT2 expression in cells (pmol/mg protein)369.419
OCT2 expression in kidney cortex (pmol/mg protein)7.67.6
In vitro metformin clearance (µl/mg protein per minute)36.7 ± 2.82.0 ± 0.1
Scaling factor (SF): [E]in vivo/[E]in vitro0.020.40
Milligrams of protein per milligram human kidney cortex weightb0.30.3
[14C]-metformin uptake (pmol/min per milligram protein)b202.1 ± 15.610.9 ± 0.7
Predicted metformin CLr,sec (ml/min) (assuming 100% of OCT2 is expressed in the plasma membrane)46.250.4
Predicted metformin CLr,sec (ml/min) (based on % OCT2 expression in the plasma membrane)152.9897.7
Predicted metformin CLr,sec (ml/min) based on plasma membrane expression and an average of twofold extrapolation of membrane resting potential based on data by Burt et al. (2016) and Koepsell and Keller (2016)305.96195.4
Predicted average CLr,sec (average of 305.96 and 195.4 ml/min) (based on plasma membrane expression and membrane resting potential)250.7
  • SF is the ratio of expression of OCT2 in the kidney cortex vs. the cells.

  • a Bouchet et al. (2003).

  • b Experimentally determined.