EXPRESS: Comparing the pharmacokinetics of GS-441524 following intravenous and oral administration of remdesivir in New Zealand cats with feline infectious peritonitis

Objectives: To compare the pharmacokinetics of GS-441524 following intravenous and oral administration of compounded remdesivir (RDV) at 30 mg/kg respectively, in cats with clinical feline infectious peritonitis (FIP), and to determine the bioavailability of GS-441524 following oral administration of compounded RDV in this population. Methods: Thirteen client-owned cats with a clinical diagnosis of FIP were prospectively recruited. To reflect real-world use, RDV (30 mg/kg) was administered via 20-minute intravenous infusion or orally (rounded up to capsule size). Plasma GS-441524 concentrations were measured at eight time points over 24 h following administration. Pharmacokinetic parameters were determined by non-compartment analysis followed by bioavailability calculation. Results: Pharmacokinetic analysis of GS-441524 following administration of oral RDV achieved a mean Cmax of 1083.36 ng/mL (SD 634.19; Coefficient of variation (CV): 59%; range 254.18 - 1834.73) at 5.33 h (SD 3.93, range 2 - 12) with a mean elimination t1/2 of 11.4 h (SD 8.00; range 4.58-27.01). In contrast, IV RDV administration produced a higher GS-441524 Cmax of 6262.54 ng/mL (SD 1118.01; CV 18%; range 5193.40-8134.39) at Tmax 0.67 h (SD 0.26; range 0.5 - 1) with elimination t1/2 of 6.8 h (SD 5.55; range 3.18-17.85). The mean relative bioavailability of GS-441524 following oral RDV was 30.13%. Bioavailability (range 12-52%) and time to maximum plasma concentrations (2-12 h) were highly variable. Conclusions & relevance: The oral bioavailability of the compounded RDV used in this study is low, highly variable and appeared lower in cats with effusive disease, although this difference was not statistically significant. Given the small non-randomised sample, results should be interpreted considering study limitations. Despite the low bioavailability, survival rates in cats treated with oral RDV are comparable to published outcome studies with injectable RDV and oral GS-441524, indicating that oral RDV is a viable treatment option when GS-441524 is not available.