Objective—To evaluate the potential utility of
poly(D,L-lactic-co-glycolic)acid (PLGA) as a long-acting
biodegradable drug delivery matrix for ivermectin
used in the prevention of heartworm disease in dogs.
Animals—30 adult female dogs.
Procedure—Microparticle formulations containing 25
weight percent (wt%), 35 wt%, and 50 wt% ivermectin
were prepared by an oil-in-water emulsion
technique with solvent extraction into excess water. A
fourth formulation, consisting of a mixture of 15 wt%
and 50 wt% ivermectin microparticles, was blended
in a 1:1 ratio to result in a 32.5 wt% ivermectin formulation.
Formulations were administered once on
Day 0 to groups of 6 dogs at a dose of 0.5 mg of ivermectin/
kg, SC. Half of the dogs in each treatment
group and 3 untreated control dogs were infected
with Dirofilaria immitis larvae 121 and 170 days after
treatment. Six months after infection, dogs were
euthanatized and necropsies were performed.
Pharmacokinetics and efficacy were investigated.
Results—Analysis of pharmacokinetic data revealed
sustained release of ivermectin during at least 287
days in 3 distinct phases: a small initial peak, followed
by release of drug through diffusion, and polymer
degradation. Untreated control dogs were all infected
with heartworms. Heartworms were not found in any
of the dogs in the ivermectin-PLGA treated groups.
Adverse clinical signs were not observed.
Conclusions and Clinical Relevance—All formulations
were 100% effective in preventing development
of adult heartworms. Results indicate that PLGA
microparticles are a promising drug delivery matrix for
use with ivermectin for the prevention of heartworm
disease for at least 6 months after treatment. (Am J
Vet Res 2004;65:752–757)
Objective—To evaluate the safety of fenbendazole in
Animals—28 six- to seven-month old domestic shorthair
Procedure—Cats were randomly assigned to 1 of 3
treatment groups or a control group (n = 7/group). Cats
in the treatment groups were given fenbendazole at a
dosage of 50, 150, or 250 mg/kg, PO, every 24 hours
for 9 days; control cats were given a placebo. A fecal
examination, coagulation tests, serum biochemical
analyses, CBC, and urinalyses were performed before
and 5, 9, and 21 days after initiation of treatment; cats
were closely monitored for adverse reactions. After the
last dose of fenbendazole was given, 4 control cats and
4 cats given fenbendazole at the highest dosage were
euthanatized, and necropsies were performed.
Results—None of the cats developed any adverse
reactions. For cats in the control and all treated
groups, laboratory test results were within reference
limits, and there were no significant differences in
results of laboratory tests among groups. No gross or
histologic lesions were identified in the control or
treated cats that were euthanatized.
Conclusions and Clinical Relevance—Fenbendazole
administered to healthy cats at a dosage 5 times the
dosage and 3 times the duration approved for use in
dogs and wild felids did not cause any acute or subacute
adverse reactions or pathologic changes. Results
suggest that cats may be safely treated with fenbendazole.
(Am J Vet Res 2000;61:330–332)