Abstract

The antimalarial agent mefloquine is currently being investigated for its potential to inhibit feline coronavirus and feline calicivirus infections. A simple, high pressure liquid chromatography assay was developed to detect mefloquine plasma concentrations in feline plasma. The assay's lower limit of quantification was 250 ng/mL. The mean ± standard deviation intra- and inter-day precision expressed as coefficients of variation were 6.83 ± 1.75 and 5.33 ± 1.37%, respectively, whereas intra- and inter-day accuracy expressed as a percentage of the bias were 11.40 ± 3.73 and 10.59 ± 3.88%, respectively. Accordingly, this validated assay should prove valuable for future in vivo clinical trials of mefloquine as an antiviral agent against feline coronavirus and feline calicivirus. However, the proportion of mefloquine binding to feline plasma proteins has not been reported. The proportion of drug bound to plasma protein binding is an important concept when developing drug dosing regimens. As cats with feline infectious peritonitis (FIP) demonstrate altered concentrations of plasma proteins, the proportion of mefloquine binding to plasma proteins in both clinically normal cats and FIP-affected cats was also investigated. An in vitro method using rapid equilibrium dialysis demonstrated that mefloquine was highly plasma protein bound in both populations (on average > 99%).

Highlights

  • Successful treatment of feline infectious peritonitis (FIP), a fatal, virulent coronavirus infection affecting predominantly younger cats, remains difficult [1]

  • The use of antiviral therapies to alter the replication of virulent forms of feline coronavirus known as feline infectious peritonitis virus (FIPV) has shown enormous hope for clinicians [3, 4]

  • Based on the UV spectra, the greatest area under the mefloquine peak was at a wavelength of 220 nm

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Summary

Introduction

Successful treatment of feline infectious peritonitis (FIP), a fatal, virulent coronavirus infection affecting predominantly younger cats, remains difficult [1]. Reviews describing the virus responsible for FIP as well as issues with diagnostics and therapeutics are available [1, 2], providing an explanation as to why re-purposing drugs used in human medicine has been largely unsuccessful in treating FIP infected cats [1]. The use of antiviral therapies to alter the replication of virulent forms of feline coronavirus known as feline infectious peritonitis virus (FIPV) has shown enormous hope for clinicians [3, 4]. The need for inexpensive, safe, antiviral medications to treat FIPV-infected cats remains.

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