Molnupiravir drug levels in cats with feline infectious peritonitis

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 (C) after a single PO dose of MPV was 38 ng/mL (SD ± 5). The mean peak serum concentration of NHC (C) after a single PO dose of MVP was 1551 ng/mL (SD ± 720). the time to reach NHC C(T) 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 ICfor 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.