Table 3

Parameters for the kinetic model of EA disposition in isolated hepatocytes

ParameterDescriptionValue
PPPV
K m uptake(μM)Michaelis-Menten constant for EA uptake 513-a  443-a
V max uptake(nmol/min/mg)Maximum facilitated uptake velocity for EA3.43-a 3.23-a
P diff(μl/min/mg)Bidirectional transmembrane clearance for EA 123-a  123-a
k 2(μM−1 · min−1)Second-order spontaneous GSH conjugation constant1263-b
K m GSH (μM)Michaelis-Menten constant for GSH in enzymatic reaction 943-b
K m EA (mM)Michaelis-Menten constant for EA in enzymatic reaction 1.23-b
V max metab(nmol/min/mg)Maximum enzymatic GSH conjugation rate30 ± 203-c 40 ± 513-c
CL efflux EA-SG (μl/min/mg)Net EA-SG efflux clearance into the extracellular compartment0.98 ± 0.183-c 0.89 ± 0.193-c
CL ves EA-SG (μl/min/mg)Net EA-SG efflux clearance into the vesicular sequestration compartment0.28 ± 0.103-c 0.24 ± 0.113-c
[GSH c t=0] (mM)Initial hepatocyte GSH concentration6.93-d 8.03-d

  • ↵3-a Obtained from [14C]EA hepatocyte uptake experiments.

  • ↵3-b From Tirona and Pang, 1999.

  • ↵3-c Fitted value (±standard deviation of the estimate) using the kinetic model.

  • ↵3-d Scaled-up from hepatocyte GSH measurements to maintain mass-balance.