Therapeutic Drug Monitoring of GS-441524 in Cats with Feline Infectious Peritonitis: Pharmacokinetic Variability and Implications for Dose Optimization.

Abstract

Remdesivir (REM) and its parent drug, GS-441524 (GS-44), are used to treat cats with feline infectious peritonitis (FIP), resulting in a survival rate of circa 85% (range 77-96%). Cats suffering from FIP exhibit complex and variable clinical presentations, which will cause concurrent variations in the pharmacokinetics (PK) of GS-44. In turn, this will vary the ability of target cells (monocytes and tissue macrophages) to absorb GS-44 in sufficient quantities to achieve optimal antiviral efficacy, resulting in full recovery. Sparse data exists to guide treatment regimens optimized for every presentation of FIP. Therapeutic Drug Monitoring (TDM) measured the GS-44 concentration in 728 blood samples from 263 cats undergoing treatment and generated 173 PK graphs. These identified individuals varied in their ability to absorb GS-44, leading to sub-optimal (11%) and supra-optimal (12%) dose-normalized plasma concentrations. Dosage alterations were suggested to guide subsequent dosages to ensure optimum GS-44 concentrations for individual cats (the clinical outcome report will be published separately). Proposed TDM target values are: area under the concentration vs. time curve (AUC), at least 220 µM·h, time per day that plasma concentration exceeds 3 µM, at least 23 h, time per day plasma concentration exceeds 10 µM, and at least 9 h.