Antiviral drugs like EIDD-2801 (molnupiravir; MPV) have been successfully used in the treatment of feline infectious peritonitis (FIP). The previous study of the pharmacokinetics of MPV in healthy cats showed promise for its use and safety. The objective was to determine the pharmacokinetics of molnupiravir in cats with naturally occurring FIP by measuring MPV and EIDD-193 (β-D-N4-hydroxycytidine; NHC) serum levels. Blood was collected from seven cats diagnosed with naturally occurring FIP treated at 1, 2, 4, 6 and 12 h post oral MPV administration and at 12 h post pill administration 7 days later. Serum concentrations of MPV and NHC were determined using a previously published high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS) method. The mean dose of MPV was 15.44 mg/kg (SD ± 1.82). The mean peak serum concentration of MPV (Cmax) after a single PO dose of MPV was 38 ng/mL (SD ± 5). The mean peak serum concentration of NHC (Cmax) after a single PO dose of MVP was 1551 ng/mL (SD ± 720). the time to reach NHC Cmax (Tmax) was 2.6 h (SD ± 1.4), and the NHC elimination half-life was 1.6 h (SD ± 1.1). Minimal drug accumulation was seen in trough concentrations following twice-daily dosing for 7 days. The low MPV levels may be explained by fast conversion to its active metabolite NHC. The mean NHC concentrations at all time points were at least 4 times the reported in vitro IC50 for feline coronavirus strains and twice-daily dosing for seven days did not lead to drug accumulation within the serum. The results support the use of MPV in the treatment of FIP, and if therapeutic drug monitoring is to be performed, NHC should be measured.
Feline herpesvirus type-1 (FHV-1) is a common viral agent associated with respiratory and ocular infections in cats. Many experimental FHV-1 challenge studies utilize the United States Department of Agriculture (USDA) strain and challenge dose developed for vaccine challenge studies. However, those FHV-1 challenge doses are likely to be considerably higher than what may be acquired naturally, potentially leading to unrepresentative results for studies other than vaccine studies. The objectives of this study were therefore to compare clinical responses to the standard FHV-1 challenge dose with those to a significantly lower challenge in naïve kittens. Secondly, the study assessed and compared clinical responses in the high- and low-dose challenge models to either a nonspecific immune stimulant or to the antiviral drug cidofovir. We found that there were no significant differences in clinical scores between high- and low-dose challenge FHV-1 groups. In addition, cats in the two dose groups responded similarly to the nonspecific immunotherapy or to cidofovir treatment. Thus, we concluded that the lower-dose challenge may be more effective for screening new drugs or vaccines for FHV-1 ocular infections in cats.
Giardia duodenalis, the primary species infecting domestic dogs, is a common enteric pathogen that sheds infectious and environmentally resistant cysts in