LAUSR.org creates dashboard-style pages of related content for over 1.5 million academic articles. Sign Up to like articles & get recommendations!

Application of Physiologically Based Pharmacokinetic Modeling to Predict the Effects of FcRn Inhibitors in Mice, Rats, and Monkeys.

Photo by mertguller from unsplash

There is a growing interest in developing inhibitors of the neonatal Fc-receptor, FcRn, for use in the treatment for humoral autoimmune conditions. We have developed a new physiologically based pharmacokinetic… Click to show full abstract

There is a growing interest in developing inhibitors of the neonatal Fc-receptor, FcRn, for use in the treatment for humoral autoimmune conditions. We have developed a new physiologically based pharmacokinetic model that is capable of characterizing the pharmacokinetics and pharmacodynamics of anti-FcRn monoclonal antibodies (mAb) in mice, rats, and monkeys. The model includes incorporation of FcRn recycling of immune gamma globulin (IgG) in hematopoietic cells in addition to FcRn recycling of IgG in vascular endothelial cells and considers FcRn turnover and intracellular cycling. The model captured antibody disposition in wild-type and FcRn-knockout mice and rats, and also predicted the effects of intravenous immune globulin and anti-FcRn mAb on IgG disposition. Simulations predicted the change in IgG clearance in response to intravenous immune globulin with good accuracy in rats (mean prediction error of 7.15% ± 7.67%). In monkeys, prediction windows for simulated IgG concentration versus time data, as generated through Monte Carlo simulation, were able to capture the effects of anti-FcRn mAb on endogenous IgG. The model may have utility in guiding preclinical evaluations of anti-FcRn therapies in development, potentially assisting in the identification of optimal dosing strategies for this emerging class of immunosuppressive drugs.

Keywords: based pharmacokinetic; mice rats; anti fcrn; physiologically based; fcrn; rats monkeys

Journal Title: Journal of pharmaceutical sciences
Year Published: 2019

Link to full text (if available)


Share on Social Media:                               Sign Up to like & get
recommendations!

Related content

More Information              News              Social Media              Video              Recommended



                Click one of the above tabs to view related content.