MechKiM parameter values for digoxin model

Description (units)ValueComment
fu,kidney0.51Predicted (Rodgers et al., 2005; Rodgers and Rowland, 2006)
OATP4C1 CLint,T (µl/min/million PTC)4.14Estimated using sensitivity analysis Allocated to OAT1/ SLC22A6 transporter in MechKiM as OATP4C1 not defined in model
P-gp Km (µM)177Same as liver/gut (Neuhoff et al., 2013b)
P-gp Vmax (pmol/min/million PTC)434Same as liver/gut (Neuhoff et al., 2013b)
P-gp REF1.51Calculated from mRNA expression data (Hilgendorf et al., 2007)
CLPD (µl/min/million PTC)0.01Estimated using sensitivity analysis and comparing simulated Freab with that predicted using static tubular reabsorption model (Scotcher et al., 2016c) and published Caco-2 data (Neuhoff et al., 2003; Zhang and Morris, 2003; Djuv and Nilsen, 2008; Fossati et al., 2008). Same value for apical and basolateral membranes in all segments of nephron
  • fu,kidney, fraction unbound in kidney; fu,urine, fraction unbound in urine; Freab, fraction reabsorbed; CLint,T, transporter intrinsic clearance; CLPD, permeability diffusion clearance; Km, Michaelis constant; MechKiM, mechanistic kidney model in SimCYP simulator; PTC, proximal tubule cells; RAF, relative activity factor; REF, relative activity factor; Vmax, maximal velocity.