ACCREDITED CPD
ACCREDITED CPD
Cyclosporine
in Canine Atopy
•
Dr Martin de Scally BVSc (Hons) MMedVet (Med)
[email protected], Hilton Veterinary Hospital , KZN.
Calneurins are calcium-dependent serine-threonine
phosphatases that activate the transcription of cytoplasmic T-cell nuclear factors (NFATc) by dephosphorylating them. The activated NFATc is then translocated into the nucleus, where it upregulates the
expression of interleukin 2 (IL-2), pro-inflammatory
cytokine which, in turn, stimulates the growth and
differentiation of T cell response. IL-2 also promotes
the differentiation of T cells into effector T cells and
into memory T cells when the initial T cell is also
stimulated by an antigen. Calcineurin is the target of a
class of drugs called calcineurin inhibitors.
Cyclosporine A is such a calneurin inhibitor. This drug
is used as an alternative to corticosteroids to control
pruritus. It reduces pruritus and cutaneous lesions. At
a dose of 5 mg/kg/day, it was found to be equally as
effective as prednisolone. Due to its large size and lipophilic nature availability of cyclosporine is greatly
improved (50%) if the micro-emulsion formulation is
used.10 Administration of cyclosporine as micro-emulsion formulation with food decreased the bioavailability by 22% and increased the individual variability of
drug absorption – thus dosing two hours before or
after a meal is recommended.
Cyclosporine is mainly absorbed from the small intestine and is metabolised in the intestine and liver by
the cytochrome P450 enzyme system.11 The drug accumulates in the skin, liver, kidneys and fat in dogs.
In controlled blinded trials 5mg/kg/day – the approved atopy dose - of cyclosporine was shown to
cause a similar reduction in canine atopic dermatitis
extent and severity index (CADESI) compared to 0.5
or 0.75 mg/kg of prednisolone or methyl prednisolone respectively. 1,9 In another controlled blinded trial
cyclosporine out performed placebo in a dose dependent fashion. 8,10 The tolerability and safety of ora