requirement for unique device specifications for each species. Nevertheless, there
are recent examples of re-formulated human SSRIs (serotonin-selective reuptake
inhibitors) for dogs. Fluoxetine (Prozac 1 ) and clomipramine (Anafranil 1 ), mar-
keted for separation anxiety in dogs (Rothenberg et al. 2009 ), and similar agents
have been investigated for stress-related urination in cats (Hart et al. 2005 ). As a
corollary, it is worth pointing out that all drug delivery systems developed for
human medicine are tested in animal species prior to evaluation in human clinical
trials. Transdermal patches developed for the human market are, however, evalu-
ated in mice, guinea-pigs and rabbits in preference to cats and dogs.
The next section of this chapter reviews technologies for a range of routes of
delivery in the main veterinary species. Physiological principles which underpin
drug delivery in veterinary medicine are then addressed, namely how drug absorp-
tion, distribution and clearance are influenced by the expression of endogenous
transporters in several species. This can explain, in part, differing pharmacokinetic
(PK) profiles of the same drug across a range of species, which in turn can assist in
optimising dosing schedules for delivery systems.
2 Controlled-Release Principles in Veterinary Medicine
As a consequence of dependence on passive diffusion as an important aspect of
their PK profile, most agents of therapeutic value are lipophilic and many are also
weak acids or bases. The pharmacological rationale for controlled- or sustained-
release (CR, SR) drug delivery is based on a principle of zero order release of the
active agent over time to achieve sustained plasma levels in the therapeutic range.
Minimising fluctuations in plasma concentration ensures that there are reduced
peaks and troughs that could lead to toxicity and sub-therapeutic delivery, respec-
tively. Maintaining sustained plasma levels is especially important in the case of
those veterinary antibacterial drugs requiring levels to be maintained above the
minimal inhibitory concentration (MIC) for much or all of the inter-dose interval,
noting that the area under the plasma concentration-time curve (AUC) can theoreti-
cally be the same for an immediate release (IR) versus an SR formulation, although
the plasma levels attained may not be optimised for long enough in the former
(Lavy et al. 2006 ).
Furthermore, the requirement for zero order release means that the rate-limiting
step for delivery must be at the level of drug release from the device. Upon release,
an assumption is made that active drug molecules can then reach the systemic
circulation. For example, in the case of nicotine transdermal patches as an aid to
smoking cessation in humans, patches release sustained concentrations of drug onto
the skin and these are rapidly absorbed with a bioavailability of 95–98% (Gore and
Chien 1998 ). Transdermal patches enable safe and efficacious nicotine delivery; a
concentrated nicotine solution placed on the skin would normally be fatal as it is
highly permeable across the stratum corneum due to its high lipophilicity.
In veterinary medicine, SR device technology is used for drugs that cross biological
82 D.J. Brayden et al.