Novel minimal physiologically-based model for the prediction of passive tubular reabsorption and renal excretion clearance
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Graphical abstract
Abbreviations
AUC
area under the plasma concentration-time profile
BCRP
breast cancer resistance protein
CD
collecting duct
Cp
plasma concentration
CLR
renal excretion clearance
CLR, filt
renal filtration clearance
CLR, int,reab
intrinsic permeability clearance in renal tubule
CLR,sec
renal secretion clearance
DT
distal tubule
fu,p
fraction of drug unbound in plasma
Freab
fraction of the drug reabsorbed in the renal tubule
Freab’
intermediate model parameter, representing the fraction of the equilibrium reached between unbound drug concentration in the plasma and urine
GFR
glomerular filtration rate
gmfe
geometric mean fold error
IVIVE
in vitro–in vivo extrapolation
LogD
octanol-buffer distribution coefficient
LoH
loop of Henle
MATE
multidrug and toxin extrusion protein
MRP
multidrug resistance protein
OAT
organic anion transporter
OCT
organic cation transporter
OATP
organic anion-transporting peptides
OCTN
organic cation/l-carnitine transporter
Papp
apparent permeability
PBPK
physiologically-based pharmacokinetic
P-gp
P-glycoprotein
PT
proximal tubule
RMSE
root mean squared error
TFR
tubular flow rate
TSA
tubular surface area
Keywords
In vitro–in vivo extrapolation
Tubular reabsorption
Renal excretion clearance
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© 2016 The Authors. Published by Elsevier B.V.