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.

PubMed

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.