Pharmacokinetics of GS-441524 following intravenous remdesivir in six cats and results of therapeutic drug monitoring during treatment of feline infectious peritonitis: 22 cases (2021–2024)

S. J. Coggins, M. Govendir, J. M. Norris, R. Malik, E. J. Hall, M. F. Thompson, B. Kimble

Objectives

This study aimed to: (1) characterise the pharmacokinetics of GS-441524 following intravenous (iv) administration of 15 mg/kg remdesivir (RDV) in client-owned cats with feline infectious peritonitis (FIP); (2) document plasma protein binding of GS-441524 in cats; (3) determine whether trough GS-441524 plasma concentrations predict ‘simple remission’ or survival to 18 months; (4) measure GS-441524 concentration in effusions relative to plasma; and (5) qualitatively assess excretion of GS-441524 in urine.

Materials and Methods

Six cats with FIP were administered 15 mg/kg iv RDV. Serial plasma GS-441524 concentrations were measured using high-performance liquid chromatography (HPLC). Twenty-two cats with FIP had trough plasma concentrations monitored over a 12-week treatment period. Simultaneous effusion and plasma GS-441524 concentrations were compared, and urine was assessed for GS-441524 excretion.

Results

The mean peak plasma concentration of GS-441524 (C_max) after a single 15 mg/kg iv dose of RDV was 2632 ng/mL (SD 862); time to reach C_max (T_max) was 1 hour (SD 0); and elimination half-life (t_1/2) was 5.14 hours (SD 0.81). GS-441524 was present in effusions (n = 3 cats) and eliminated in urine following treatment (n = 6 cats). Assessment of the predictive relationship between median GS_TC and achieving ‘simple remission’ failed to demonstrate a significant correlation.

Clinical Significance

This study supports the use of RDV and GS-441524 for FIP treatment and suggests that population pharmacokinetic modelling is required to better explore the utility of therapeutic drug monitoring of GS-441524.

Read the full article at: https://onlinelibrary-wiley-com.ezproxy.library.wisc.edu/doi/10.1111/jsap.13849