transendothelial electrical resistances of endothelial monolayers (even when
co-cultured with astrocytes or astrocyte-conditioned media) (Grant et al. 1998 ;
Terasaki et al. 2003 ). In addition, the cell isolation process is both lengthy and
expensive and there is restricted tissue availability. The most complete set of
mapped ABC transporters on the BBB is from rat brain microvessels (Lo ̈scher
and Potschka 2005 ; Roberts et al. 2008 ), where MDR, ABCG2 and ABCC4 were
expressed on the apical membrane, while ABCC1 was weakly expressed on the
basolateral membrane. For companion animals, future advances will be assisted if
new species-specific antibodies become available, together with further study of
expression and function of ABC transporters in isolated capillaries and advanced
cultured endothelial cell models (e.g. Fletcher et al. 2006 ).
5 Conclusions
Veterinary medical research has a long and distinguished history in the design of
species-specific drug delivery devices and formulations. Development of commer-
cially-viable and therapeutically effective implantable devices for production ani-
mals to release steroids, anthelmintics and antibacterial drugs has required creative
designs using relatively cheap polymers. Spot-on formulations of anthelmintics for
small animals take advantage of using the skin’s sebaceous glands as a drug-
secreting reservoir, notwithstanding the integumental heterogeneity of different
species. Use of skin patches has been translated to a minor extent from human
medicine and has found a limited niche in post-operative pain control. Long-acting
SR injectable biodegradable formulations are more commonly used in veterinary
medical applications than in humans. Rare, but important examples from exotic
species provide both challenges and opportunities (Hunter and Isaza 2002 ).
Finally, endogenous control of the fate of veterinary drugs on entering the
body and their subsequent distribution and elimination involve understanding the
BloodabcdFig. 4The role ofP-gpinivermectinPK.(a) Oral absorption is limited byP-gp efflux to the intestinal
lumen from intestinal enterocytes. (b)IncreasedP-gp-mediated secretion into bile for enterohepatic
shunting occurs at the bile canaliculi bordered by hepatocytes. (c)P-gp on renal proximal tubule
epithelia causes ivermectin secretion from blood into renal tubular fluid. (d)P-gp on blood–brain
barrier endothelia prevents ivermectin access to the CNS from the blood. (a–c) act to prevent access to
or to remove ivermectin from the blood. Note that blood concentrations impact on subsequent parasite
exposure and thatP-gp expression on parasite membranes may also contribute to ivermectin
resistance (Lespine et al. 2008 )
Drug Delivery Systems in Domestic Animal Species 103