Infliximab Treatment Does Not Lead to Full TNF-α Inhibition: A Target-Mediated Drug Disposition Model

2021 ◽  
Author(s):  
David Ternant ◽  
Marc Pfister ◽  
Olivier Le Tilly ◽  
Denis Mulleman ◽  
Laurence Picon ◽  
...  
Keyword(s):  
Drug Disposition ◽  
Infliximab Treatment ◽  
Tnf Α ◽  
Target Mediated Drug Disposition ◽  
Disposition Model

Application of Target-Mediated Drug Disposition Model to Small Molecule Heat Shock Protein 90 Inhibitors

2013 ◽  
Vol 41 (6) ◽  
pp. 1285-1294 ◽  
Author(s):  
Shinji Yamazaki ◽  
Zhongzhou Shen ◽  
Ying Jiang ◽  
Bill J. Smith ◽  
Paolo Vicini
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Small Molecule ◽  
Drug Disposition ◽  
Heat Shock Protein 90 ◽  
Target Mediated Drug Disposition ◽  
Disposition Model

scholarly journals Population pharmacokinetics and pharmacodynamics of a novel vascular adhesion protein-1 inhibitor using a multiple-target mediated drug disposition model

2020 ◽  
Author(s):  
Nelleke Snelder ◽  
Sven Hoefman ◽  
Alberto Garcia-Hernandez ◽  
Hartmut Onkels ◽  
Tobias E. Larsson ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Healthy Volunteers ◽  
Diabetic Kidney Disease ◽  
Drug Disposition ◽  
Diabetic Kidney ◽  
Adhesion Protein ◽  
Target Mediated Drug Disposition ◽  
Vascular Adhesion ◽  
Disposition Model ◽  
Vascular Adhesion Protein 1

Abstract ASP8232 is a novel inhibitor of vascular adhesion protein-1 that was under evaluation for reducing residual albuminuria in patients with diabetic kidney disease. To characterize the pharmacokinetics (PK) of ASP8232 and its effect on vascular adhesion protein 1 (VAP-1) plasma activity and VAP-1 concentrations (pharmacodynamics, PD) in an integrated and quantitative manner, a target mediated drug disposition model was developed based on pooled data from four completed clinical trials with ASP8232 in healthy volunteers, and in patients with diabetic kidney disease and diabetic macular edema, respectively. In this model, the binding of ASP8232 to its soluble and membrane-bound target in the central and peripheral compartments were included. The model was able to adequately describe the non-linear PK and PD of ASP8232. The observed difference in PK between healthy volunteers and renally impaired patients could be explained by an effect of baseline estimated glomerular filtration rate on ASP8232 clearance and relative bioavailability. The relationship between ASP8232 concentration and VAP-1 inhibition was successfully established and can be applied to simulate drug exposure and degree of VAP-1 inhibition for any given dose of ASP8232 across the spectrum of renal function.

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