student profile: Dr Aaron Izes


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Thesis work

Thesis title: Determination of mefloquine�s intrinsic clearance by feline microsomes; could this be a suitable treatment for Feline Infectious Peritonitis (FIP)?

Supervisors: Merran GOVENDIR , Benjamin KIMBLE, Kong LI , Jacqueline NORRIS

Thesis abstract:

Feline infectious peritonitis (FIP) is a systemic, fatal, viral-induced immune-mediated disease that affects cats globally. The disease is caused by virulent biotypes of feline coronaviruses (FCoV), known as the feline infectious peritonitis virus (FIPV). Traditionally, the treatment of FIP has centered on the use of immunosuppressive therapies. Yet, although some immunomodulatory therapeutic agents temporarily dampen clinical signs, there are no treatments that address the underlying problem of viral replication. Recent in vitro studies seeking an efficacious FCoV treatment investigated 19 candidate compounds used commonly in the treatment of other coronavirus infections. One of these compounds, mefloquine, a drug typically used in the treatment and prophylaxis of malaria in humans, showed great promise in that it substantially reduced the viral load of FIPV in infected Crandall feline kidney cells without cytotoxic effects at low mefloquine concentrations. This evidence suggests that mefloquine should be considered for further investigation as a potential treatment option for FIP. However, the careful consideration of the idiosyncracies of feline hepatic metabolism is required for any proposed treatment in cats in order to minimise any potential for harm. In cats, some therapeutic agents are known to have issues with hepatic metabolism, especially the reduction in activity of some conjugative glucaronyl transferase iso-enzymes and result in delayed elimination and consequent toxicity, such as is seen with paracetamol, propofol, carprofen and acetylsalicylic acid. As there are no pharmacokinetic studies on the use of mefloquine in the cat, the overall aim of this project is to use an in vitro model of feline hepatic metabolism to ascertain whether mefloquine is likely to accumulate in the cat.
 

Selected grants

2016

  • Determination of mefloquine’s intrinsic clearance by feline microsomes; could this be a suitable treatment for Feline Infectious Peritonitis (FIP)?; Govendir M, Norris J, Izes A; Feline Health Research Fund (FHRF)/Research Grant.

Selected publications

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Conferences

  • Izes, A., Norris, J., Govendir, M. (2016). Determination of mefloquine’s intrinsic clearance by feline microsomes; could this be a suitable treatment for feline infectious peritonitis (FIP)? Australian and New Zealand College of Veterinary Scientists, N/A: N/A.

2016

  • Izes, A., Norris, J., Govendir, M. (2016). Determination of mefloquine’s intrinsic clearance by feline microsomes; could this be a suitable treatment for feline infectious peritonitis (FIP)? Australian and New Zealand College of Veterinary Scientists, N/A: N/A.

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