TABLE 1

Concentrations, transfer rates, and clearance values

Imaging substratesP
BOPTAMEB
Concentrations (µM)
 End of perfusion period
  Cin20064
  Cout185 ± 35 ± 20.002
  Cliver574 ± 882,486 ± 3620.002
  CEC62 ± 2032 ± 70.004
  CHC78%441 ± 782,036 ± 3890.002
  CHC100%566 ± 992,610 ± 4980.002
  CBC72 ± 9417 ± 490.002
  Cbile16,791 ± 2,08597,017 ± 11,2890.002
Transfer rates (nmol/min)
 End of perfusion period
  v464 ± 801,797 ± 610.002
  vin561 ± 811,819 ± 540.002
  vbile (nmol/min)390 ± 84990 ± 1660.002
  vef97 ± 722 ± 80.002
Clearance parameters
 End of perfusion period
  CLH (mlKHB/min)2.3 ± 0.427.8 ± 0.90.002
  CLin (mlKHB/min)2.8 ± 0.428.1 ± 0.80.002
 Perfusion and rinse periods
  CLbile (mlHC/min)0.89 ± 0.250.47 ± 0.150.009
 Rinse period
  CLef (mlHC/min)0.18 ± 0.030.01 ± 0.010.002
  CLbile + CLef (mlHC/min)1.1 ± 0.30.5 ± 0.10.004
Concentration ratios
  RHC/EC4 ± 233 ± 190.002
  Rbile/HC31 ± 645 ± 120.03
  RHV/HC0.006 ± 0.0010.0003 ± 0.00010.002
  Rbile/EC299 ± 1113218 ± 11090.002

  • CHC100% is CHC78% multiplied by 100/78. Substrate removal rate from sinusoids (v), hepatocyte influx rate (vin), bile excretion rate (vbile), and efflux rate back into sinusoids (vef). Hepatocyte-to-extracellular concentration ratio (RHC/EC) were measured at T0 in the absence of hepatocyte efflux. Bile-to-hepatocyte concentration ratio (Rbile/HC) was the slope of the relationship between CHC (x-axis) and Cbile (y-axis) during the perfusion and rinse periods. Hepatic vein–to-hepatocyte concentration ratio (RHV/HC) was the slope of the relationship between CHC (x-axis) and Cef (y-axis) during the rinse period. Bile-to-extracellular concentration ratio (Rbile/EC) was the maximal ability of transporters to concentrate substrates from the EC to bile compartment at the end of the perfusion period. CLH and CLin were expressed in ml of Krebs-Henseleit Bicarbonate (KHB) solution/min (mlKHB/min). CLef and CLbile were expressed in ml of hepatocytes (HC)/min (mlHC/min).