Transdermal patches delivering a range of passively-absorbed lipophilic drugs
have been successfully developed for human medicine (Ball and Smith 2008 ).
Human patches marketed over a 30-year period have incorporated scopolamine,
oestrogen, clonidine, nicotine, fentanyl, buprenorphine and oxybutinin. While
research in human transdermal patches has recently led to marketing of complex
patches for lignocaine and fentanyl using iontophoresis to assist absorption, veteri-
nary patch research has more limited objectives. This is due to large inter-species
variation between human, ovine, porcine, bovine and murine skin structure and
composition (Hammond et al. 2000 ), reflected by lack of cross-species prediction of
barrier properties of thestratum corneum. Together with the presence of scales,
feathers, fleece, hair or fur, uncooperative subjects, risk of oral ingestion and the
lack of predictive PK-pharmacodynamic (PD) relationships (Riviere and Papich
2001 ), the limitations are considerable. Nevertheless, the niche opportunity to dose
animals post-operatively with analgesics to achieve sustained blood levels over a
2–3 day period is attractive to veterinarians. Hofmeister and Egger ( 2004 ) carried
out a meta-analysis of selected canine and feline patch studies where the mu-opioid
agonist, fentanyl, was the active constituent. They concluded that, although there
was large variability in the rate and extent of absorption between animals of the
same species and a lack of a defined relationship between plasma concentrations
and pain relief, such patches may provide an alternative option for relieving pain in
small animals. The objective therefore is to provide sustained absorption for potent
agents such as fentanyl, which have short elimination half-lives.
Despite this, a recent study of fentanyl patches used to reduce post-operative pain
in dogs reported no analgesic benefit over and above a standard injected dose of
morphine, while costs of treatment were higher for the patch system (Egger et al.
2007 ). Transdermal fentanyl patches have also been used in pigs (Malavasi et al.
2006 ) and horses (Mills and Cross 2007 ) with varying degrees of success. Transder-
mal delivery of the mu-opioid partial agonist, buprenorphine, to cats also failed to
provide analgesia despite reaching significant plasma concentrations (Murrell et al.
2007 ). Regarding other drugs, lignocaine patches have been placed on the skin of
cats (Ko et al. 2008 ), dogs (Ko et al. 2007 ) and horses (Bidwell et al. 2007 ) for
periods of up to 72 h. In each case, although adverse events were minimal, plasma
levels were low. Overall, therefore transdermal patches have not made a significant
impact in veterinary medicine, but despite this, the topical route of delivery
is increasingly popular. Mills and Cross ( 2006 ) have warned, however, that products
need to be specifically formulated for the skin of the target species and that, in
addition, extrapolation of drug PK and PD properties between species is unlikely to
lead to successful outcomes. It is worth noting therefore that the increase in veteri-
nary transdermal formulations that are compounded in unregulated US pharmacies
is not based on any objective evidence of efficacy. Table 4 indicates selected
formulations for veterinary topical delivery in common use, of which the majority
are efficacious spot-ons. In 2008, in a disappointing assessment of veterinary pharma
innovation, it was stated there were more than 12 undifferentiated iterative prescrip-
tion flea-managing marketed products, the majority with similar dosing frequency,
mode of administration and mechanism of action (Rothenberg et al. 2009 ).
90 D.J. Brayden et al.