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Published on: July 6, 2013
Pharmacokinetics of Molnupiravir in Cats with Naturally Occurring Feline Infectious Peritonitis
Petra Černá1, Luke Wittenburg2, Jennifer Hawley1
1Department of Clinical Sciences, Colorado State University, Fort Collins, CO 80523, USA.
Abstract:
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.
Insights
Molnupiravir (MPV) shows promising pharmacokinetics in cats with feline infectious peritonitis (FIP). Its active metabolite, NHC, reached concentrations effective against the virus, supporting MPV use for FIP treatment.
Area of Science:
- Veterinary Pharmacology
- Antiviral Drug Development
- Feline Infectious Diseases
Background:
- Feline infectious peritonitis (FIP) is a severe disease in cats.
- Antiviral drugs, including molnupiravir (MPV), are being investigated for FIP treatment.
- Previous studies indicated MPV's potential safety and efficacy in healthy cats.
Purpose of the Study:
- To determine the pharmacokinetics of molnupiravir (MPV) and its active metabolite, EIDD-193 (NHC), in cats with naturally occurring FIP.
- To assess MPV and NHC serum levels during treatment in FIP-affected cats.
- To evaluate potential drug accumulation with repeated dosing.
Main Methods:
- Seven cats with naturally occurring FIP were administered oral MPV.
- Serum samples were collected at various time points post-administration (1, 2, 4, 6, 12 hours, and 7 days later).
- MPV and NHC concentrations were quantified using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS).
Main Results:
- Mean peak serum concentration (Cmax) of MPV was 38 ng/mL, with rapid conversion to NHC.
- Mean peak serum concentration (Cmax) of NHC was 1551 ng/mL, with a Tmax of 2.6 hours and a half-life of 1.6 hours.
- NHC concentrations exceeded the in vitro IC50 for feline coronavirus strains, and no significant drug accumulation occurred with twice-daily dosing for 7 days.
Conclusions:
- Molnupiravir (MPV) demonstrates favorable pharmacokinetics in cats with FIP.
- The active metabolite, NHC, achieves therapeutic concentrations supporting MPV's use in FIP treatment.
- Therapeutic drug monitoring for MPV in FIP cats should focus on measuring NHC levels.

