Mechanism-based modeling of the effect of a novel inhibitor of vascular adhesion protein-1 on albuminuria and renal function markers in patients with diabetic kidney disease

• DOI: 10.1007/s10928-020-09716-x
• Publication Date: 2020-09-14T20:02:42Z
• Authors: Sven Hoefman; Nelleke Snelder; Martijn van Noort; Alberto Garcia-He...; Hartmut Onkels; Tobias E. Larsson; Kirsten R. Bergmann
• Keywords: Albuminuria; Pharmacodynamics

Abstract The vascular adhesion protein-1 (VAP-1) inhibitor ASP8232 reduces albuminuria in patients with type 2 diabetes and chronic kidney disease. A mechanism-based model was developed to quantify the effects of on renal markers from a placebo-controlled Phase study diabetic disease 12 weeks treatment. incorporated available pharmacokinetic, pharmacodynamic (plasma VAP-1 concentration activity), serum urine creatinine, cystatin C, albumin excretion rate, urinary albumin-to-creatinine ratio, volume information an integrated manner. Drug-independent time-varying changes different drug could be quantified for these using model. Through simulations, this provided opportunity dissect relationship longitudinal association between estimated glomerular filtration rate pharmacological ASP8232. drug-independent may useful as starting point other compounds affecting same biomarkers similar time scale.