Comparative and Veterinary Pharmacology

(Elliott) #1

An in vitro high-throughput membrane coated fibre array technique using gas
chromatography/mass spectrometry (GC/MS) has been developed in our laboratory
to assess absorption of chemicals and drugs through skin. The approach is well
suited for high throughput screening and is predictive of dermal chemical absorp-
tion as well as chemical mixture interactions (Xia et al. 2007 ; Baynes et al. 2008 ).
Further refinement of such approaches will allow rapid identification of drug
candidates optimised for delivery by a selected route, as well as assessing the effect
of formulation excipients on rate and extent of delivery without a requirement to
conduct in vivo trials.
The dramatic impact of automation in transforming drug development in the
pharmaceutical industry in only two decades is remarkable. It is difficult to project
forward these developments into future forecasts, but it is certain that very large
libraries of compounds with specific activities screened for adverse effects will
become available for clinical development in veterinary therapeutics. An example
of how technology has enabled rapid advances in genomics is the fact that a mere 20
years ago it took one year to manually sequence a gene with 10,000 base pairs. This
can now be accomplished in less than 2 weeks and, moreover, at a fraction of the
cost. This technology will continue to be optimised, so that time and cost per base-
pair will continue to decrease. As indicated above, developments in bioinformatics
in association with in silico pharmacology and toxicology analyses will allow data
to be interpreted with greater speed and accuracy, thus enabling identification of
more candidate drugs with appropriate safety and efficacy profiles in target species.


8 Increased Ability to Control and Target Drug Delivery

Although each of the above developments, with the exception of the continued
development of high-throughput systems, could revolutionise veterinary therapeu-
tics, the area with the greatest likelihood of impacting within the next two decades
is controlled and targeted drug delivery. This topic is reviewed in chapter, “Drug
Delivery Systems in Domestic Animal Species” of this volume. Innovations now
close to adoption include the addition of polymer groups, such as polyethylene
glycol (PEG), to protein and peptide drugs to prolong systemic residence times
(Greenwald 2001 ). In addition, increased SAR knowledge has allowed the selection
of drug molecules with longer terminal half-lives, avoiding the need for frequent
administration.
When increased knowledge of the determinants of the mechanisms of cellular
uptake of nanoparticles is obtained (Ryman-Rasmussen et al. 2007 ), nano-based
therapeutics, targeted to specific cell types will become possible. Electrically-
assisted transdermal delivery systems developed a decade ago and now in use for
some human applications, may also have applications in veterinary medicine
(Riviere and Heit 1997 ). One innovation was the transdermal delivery of charged
or peptide drugs not otherwise able to penetrate the stratum corneum barrier.
Controlled-release transdermal patches and formulations for compounds such as


204 J.E. Riviere

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