SELECTIVE RENAL DISPOSITION OF THE CALCINEURIN INHIBITORS VOCLSOPORIN, CYCLOSPORINE, AND TACROLIMUS (ERA-EDTA 2023) - Apr 15, 2023 - Abstract ##2989; Pres time: Jun 17, 2023; 02:51 PM - 02:56 PM; Location: Amber 6; "CL CL/F fu Expected CLr (GFR*fu) CLr Cyclosporine A 210-240 mL/min 500-600 mL/min 10% 12.5 mL/min 1.48 mL/min Tacrolimus 37.5 mL/min NA 1% 1.25 mL/min 0.014 mL/min Voclosporin NA 1060 mL/min 3% 3.75 mL/min 7.82 mL/min CL, clearance; Clr, renal clearance; F, bioavailability; fu, fraction unbound in plasma; GFR, glomerular filtration rate; NA, not applicable Desorption and Ionization Mass Spectrometry Imaging (MALDI-MSI). MALDI-MSI revealed differential retention and distribution of CSA, TAC and VCS in mice, consistent with their respective renal clearances in humans. Higher drug exposure and >90% renal reabsorption was observed for both CSA and TAC in this study, whereas the renal handling of VCS suggested a significant component of tubular secretion. The higher rate of secretion and lower overall exposure of kidney tissue to VCS may be associated with an improved safety profile when compared to the more diffuse distribution and greater renal retention of CSA..."
Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Renal Disease • Solid Organ Transplantation • Transplantation
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Simon Zhou1; Krishani Kumari Rajanayake2; Miao He2; Bo Wen2; Ankha Lkhagva2; Ernie Yap1; Duxin Sun2; Jennifer L. Cross1; Kory Engelke1; Robert B. Huizinga1
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