Message Number: FHL12717 | New FHL Archives Search
From: Sukie Crandall
Date: 2011-01-06 20:55:14 UTC
Subject: [ferrethealth] abstract
To: fhl <>

The full paper is available for free at

so may be useful for some vets dealing with ferrets
who have certain serious lung issues.


J Pharmacol Exp Ther. 2011 Jan 4. [Epub ahead of print]
In Vivo Characterisation of GSK256066, A High Affinity Inhaled=20
Phosphodiesterase 4 Inhibitor.
Nials AT, Tralau-Stewart CJ, Gascoigne MH, Ball DI, Ranshaw LE,=20
Knowles RG.
1 GlaxoSmithKline;
Oral PDE4 inhibitors have demonstrated clinical efficacy in chronic=20
obstructive pulmonary disease and asthma. Pre clinical and clinical=20
investigation of inhaled PDE4 inhibitors is ongoing. GSK256066 is an=20
exceptionally high affinity and selective inhibitor of PDE4 designed=20
for inhaled delivery. The aim of these studies was to investigate the=20
potency, duration of action and therapeutic index of GSK256066 in=20
animal models of pulmonary inflammation. The effects of=20
intratracheally administered GSK256066 were investigated in rat=20
lipopolysaccharide (LPS) and ovalbumin induced models of acute,=20
pulmonary inflammation. In some studies, fluticasone propionate (FP)=20
was included as a comparator. The Therapeutic Index (anti-inflammatory=20
effect versus emesis) of GSK256066 was studied in ferrets where acute=20
pulmonary inflammation was induced with inhaled LPS. In rats,=20
GSK256066 and FP caused significant (p<0.05) inhibition of LPS-induced=20
pulmonary neutrophilia. The duration of action of GSK256066 at 10 x=20
ED50 dose (10=CE=BCg/kg) was 12h. GSK256066 and FP also inhibited LPS-
induced increases in exhaled nitric oxide (ED50 35 =C2=B5g/kg & 92 =CE=BCg/=
respectively). In addition, GSK256066 inhibited pulmonary eosinophilia=20
in rats exposed to ovalbumin (ED50 0.4 =CE=BCg/kg). In ferrets, inhaled =

GSK256066 inhibited LPS-induced pulmonary neutrophilia (ED50 18 =CE=BCg/kg)=
and no emetic episodes were observed. Thus, GSK256066 may have an=20
improved therapeutic index compared to oral PDE4 inhibitors e.g.=20
cilomilast and roflumilast. In summary, GSK256066 demonstrates potent=20
and long-lasting anti-inflammatory effects in animal models of=20
pulmonary inflammation and does not induce emetic episodes in ferrets.=20
GSK256066 has potential as an inhaled therapeutic for the treatment of=20
asthma and Chronic Obstructive Pulmonary Disease.
PMID: 21205924 [PubMed - as supplied by publisher]


Sukie (not a vet)

Recommended ferret health links:
all ferret topics:

"All hail the procrastinators for they shall rule the world tomorrow."
(2010, Steve Crandall)


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