TABLE 3.
MechKiM parameter values for digoxin model
| Description (units) | Value | Comment |
|---|---|---|
| fu,kidney | 0.51 | Predicted (Rodgers et al., 2005; Rodgers and Rowland, 2006) |
| fu,urine | 1 | |
| OATP4C1 CLint,T (µl/min/million PTC) | 4.14 | Estimated using sensitivity analysis Allocated to OAT1/ SLC22A6 transporter in MechKiM as OATP4C1 not defined in model |
| OATP4C1 RAF/ REF | 1 | |
| P-gp Km (µM) | 177 | Same as liver/gut (Neuhoff et al., 2013b) |
| P-gp Vmax (pmol/min/million PTC) | 434 | Same as liver/gut (Neuhoff et al., 2013b) |
| P-gp REF | 1.51 | Calculated from mRNA expression data (Hilgendorf et al., 2007) |
| CLPD (µl/min/million PTC) | 0.01 | Estimated 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.