A dual-strategy approach to improve GS-441524 therapy in feline infectious peritonitis: salt engineering and orally disintegrating tablet development.

Abstract

Feline infectious peritonitis (FIP) is a fatal disease caused by mutations in feline enteric coronavirus, posing significant challenges in feline medicine. GS-441524 (GS), the active metabolite of remdesivir, has demonstrated efficacy in FIP treatment. However, its poor solubility and low oral bioavailability require high doses for therapeutic effect, limiting its practicality. This study aimed to overcome these limitations by transforming GS into hydrochloride (GS-H) and sulfate (GS-S) salts, substantially improving solubility and bioavailability. Among these, GS-S exhibited 58-fold higher solubility and 3.8-fold higher plasma concentration than GS, making it the preferred candidate for further development. To overcome challenges in feline oral drug administration, GS-S-based orally disintegrating tablet (ODT) was developed to disintegrate rapidly in the feline oral cavity, ensuring easier administration and accurate dosing. The formulation, comprising mannitol, microcrystalline cellulose, crospovidone, and polyvinylpyrrolidone, disperses in water within 7.7 s, providing an alternative when direct oral administration is challenging. The GS-S-based ODT (GS-S ODT) maintained pharmacokinetic properties comparable to GS-S powder, confirming its potential as a practical alternative. This study explores advancements in GS formulation by integrating enhanced bioavailability with improved administration convenience, providing a foundation for more effective and accessible FIP treatments to address key challenges in feline healthcare.