tablets for dogs (Thombre 2004 ). Examples of flavoured chewable tablets designed
for dogs include beef-flavoured ivermectin/pyrantel (Clark et al. 1992 ), beef-
flavoured fluoxetine (Simpson et al. 2007 ), and liver-flavoured COX-2 selective
NSAIDs (Pollmeier et al. 2006 ). Given the unpredictable flavour preferences of
small animals, taste-and odour-masking technologies also have a role to play. Other
options include buccal films and gels, flavoured treats and medications in fluids.
As a unique equine delivery formulation, an oral paste containing a mixture of
ivermectin and praziquantel achieved good efficacy and was convenient to admin-
ister (Rehbein et al. 2007 ). This combination is now successfully marketed as,
for example, EquimaxTMPaste (Pfizer Animal Health) and Zimecterin 1 Gold
(Merial). The incorporation of carbimazole, a pro-drug of methimazole, used in
the treatment of hyperthyroidism in cats, into a CR formulation provides an
example of extending duration of action in companion animal medicine to allow
once daily dosing while avoiding significant accumulation (Frenais et al. 2009 ).
Bioavailability was similar for conventional and CR tablets, but was increased in
fed versus fasted cats. Aragon et al. ( 2009 ) achieved sustained plasma concentra-
tions of morphine in dogs (over 24 h) using a spheroidal formulation that provided
both immediate- and CR components. However, high inter-animal variability is
likely to limit the clinical use of this particular formulation.
3.2 Airway Delivery: Pulmonary and Nasal
Experimental animals have been used to investigate airway delivery of drugs,
vaccines, inhalational anaesthetics, and toxins. Indeed, the image of the cigarette-
smoking Beagle is one which generated a huge debate over animal experimentation
as well as hazards of tobacco smoking. Use of the respiratory tract as a conduit for
drug delivery to the systemic circulation in animals lags behind R&D in its human
counterpart because of cost, limited markets, and technical issues of species and
breed specific device design. Nonetheless, inhaled delivery of insulin to Beagles
has been achieved using a modified endotracheal inhaler. This yielded insulin blood
concentrations of the same order as those obtained with subcutaneous (s.c.) admini-
stration (Edgerton et al. 2009 ). It seems that dog models may also be used in the
development pathway for pulmonary delivery in human medicine. For example, a
growth-hormone-releasing factor mimetic formulated as dry powder spray-dried
microparticles and designed for humans was administered intra-tracheally to dogs
to yield 41% bioavailability relative to the subcutaneous (s.c.) route (Jansen et al.
2004 ). This type of data can be useful as a precursor to subsequent human clinical
trials. Recently, inhalation of short-acting insulin aerosol by cats also reduced blood
glucose concentration and it was suggested that this option could be available
instead of injections, in cases where dietary changes and hypoglycaemic drugs
were advocated (DeClue et al. 2008 ). The failure of the pulmonary human insulin
product Exubera 1 , suggests that there are major issues for the entire field of
systemic delivery by this route no matter what the species.
86 D.J. Brayden et al.