antibiotic injections investigated in dogs include oxytetracycline solutions with
organic solvent excipients (i.m) (Kikuvi et al. 2001 ). Smith et al. ( 2008 ) investi-
gated the PK of a CR liposome-encapsulated parenteral product containing the
opioid analgesic drug hydromorphone. Compared to IV dosing, the apparent termi-
nal half-life of hydromorphone in the CR formulation was increased from 0.52 h to
approximately 30 h.
SR techniques and devices have been evaluated more frequently for companion
animals than for production animals. One of the aims of such delivery systems is to
reduce systemic side effects associated with potent drugs while maintaining efficacy.
For example, biodegradable implants impregnated with cisplatin have been used
with some success to prevent recurrent osteosarcoma in dogs following limb ampu-
tation (Withrow et al. 2004 ), and there have been attempts to implant polymethyl-
methacrylate beads containing gentamycin to treat canine femur osteomyelitis
(Wahlig et al. 1978 ). As a potential contraceptive strategy, treatment with a
6-month biodegradable implant containing the gonadotrophin-releasing hormone
(GnRH) agonist, deslorelin (Peptech, Australia), suppressed the activity of the
pituitary-gonadal axis leading to reduced testosterone production in male dogs within
1 month (Junaidi et al. 2007 ). Finally, there is considerable interest in examining SR
injectables in veterinary species using excipients selected from the high viscosity
lipophilic sugar (sucrose acetate isobuyrate, SAIB), amphipathic molecules (PEG
(poly(ethylene) glycol)-PLA (poly(lactic) acid)-PEG) co-polymers and biodegrad-
able PLA/PLG (polylactide-co-glycolide). The SABER-TM technology (Durect
Corp, USA) consists of SAIB with a small amount of organic solvent with PLA
polymer and its unique features permit a sol–gel conversion in situ, which forms a
semi-solid depot SR implant. The simple “mix and fill” scaleable manufacturing
process is a feature of this application and it is less expensive than typical micropar-
ticle technologies. In a study in mares comparing oestradiol release from microparti-
cle and SABER-TMformulations, similar plasma levels were detected (Johnson et al.
1999 ). Issues to address to increase acceptance of non-polymeric and polymeric in
situ implant technologies in veterinary medicine include improving drug loading,
replacing organic solvents and identifying sufficiently potent drugs that do not
require high injection volumes (Matschke et al. 2002 ).
4 Endogenous Regulation: The Role of Drug Transporters
in Regulating Delivery
The foregoing has examined the challenges involved in developing delivery for-
mulations and devices for administering veterinary drugs by particular routes to
optimise PK and PD profiles. The numerous endogenous transport mechanisms that
contribute to drug absorption and distribution across epithelial and endothelial cell
barriers comprise another important aspect of drug delivery. Thus, exogenous
delivery systems and endogenous drug transporters are linked if the drug is a
Drug Delivery Systems in Domestic Animal Species 97