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Quantification of GS-441524 concentration in feline plasma using high performance liquid chromatography with fluorescence detection

W21-006: Quantification of GS-441524 concentration in feline plasma using high performance liquid chromatography with fluorescence detection, Veterinary Quarterly, 43:1, 1-9, DOI: 10.1080/01652176.2023.2246553
Benjamin Kimble, Sally J. Coggins, Jacqueline M. Norris, Mary F. Thompson & Merran Govendir (2023)
An EveryCat-Funded Study

The EveryCat Health Foundation has shown a strong commitment to supporting studies related to Feline Infectious Peritonitis (FIP), a once-thought incurable viral disease. Through an EveryCat grant, a research team from the Sydney School of Veterinary Medicine in Australia recently published a study looking at an alternative and cost-effective way to monitor drug concentrations in naturally infected FIP cats.

Remdesivir is an anti-viral drug that is approved in humans for the treatment of SARS-CoV-2 (COVID-19) and has shown promise along with its active metabolite GS-441524 for treatment of cats infected with FIP. There are currently no feline-approved products of these antiviral compounds, but these medications can be legally obtained in Australia as well as the UK.

The Sydney research group has been actively investigating Remdesivir for treatment in naturally infected FIP client-owned cats. However, no studies have been undertaken to determine the bioavailability of GS-441524 after administration of Remdesivir to feline patients. This study investigated the development and validation of a method to quantify GS-441524 in plasma after IV (intravenous) or SC (subcutaneous) Remdesivir (10-15 mg/kg BW) administration.

A total of 12 cats samples were analyzed from FIP infected cats that were enrolled in a Remdesivir clinical trial conducted at Sydney. GS-441524 was analyzed via a fluorescence monitor. To validate this method, plasma samples from both FIP-free and infected cats with and without administered medications such as dexamethasone, medetomidine, maropitant, amoxicillin-clavulanate and gabapentin were also evaluated. The other medications chosen were medications commonly prescribed for supportive care or sedation in FIP infected patients. Chromatograms were then plotted based on fluorescence detection range on the Y axis and minutes to detection on the X axis.

Mass spectrometry has previously been utilized to detect GS-441524 in feline plasma, but this method is costly. The alternative technique employed in this study successfully identified GS-441524 as the major circulating plasma metabolite after Remdesivir administration. This result is similar to what has been described in humans. An optimum fluorescence detection range (optimized to λex: 250 nm; λem: 475 nm) was determined to detect GS-441524 against common medications prescribed by clinicians to supportively treat FIP-infected cats. The study also identified excellent sensitivity for detection of Remdesivir and its other metabolites. Limitations of the study included a small number of analyzed samples and the use of external calibration (an internal standard (IS) could not be identified for the fluorescent spectrum of GS-441524).

This study successfully showed that GS-441524 could be identified in plasma via fluorescence detection at least up to 24 hours after administration of Remdesivir (at a standard 10-15 mg/kg BW dose). These results could be used in the future for therapeutic monitoring (such as determining plasma trough levels) as well as additional pharmacokinetic studies of Remdesivir and/or GS-441524 in cats. ~BJP

See Also:

Coggins SJ, Norris JM, Malik R, Govendir M, Hall EJ, Kimble B, Thompson MF. Outcomes of treatment of cats with feline infectious peritonitis using parenterally administered remdesivir, with or without transition to orally administered GS-441524. J Vet Intern Med. 2023 Sep-Oct;37(5):1772-1783. doi: 10.1111/jvim.16803. Epub 2023 Jul 13. PMID: 37439383; PMCID: PMC10473006.