Page 572 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

VetBooks.ir Chapter 43

Macrocyclic Lactone Endectocides

Sharon M. Gwaltney-Brant, Camille DeClementi and Ramesh C. Gupta

INTRODUCTION popular because of their efficacy and wide margin of
safety. Ivermectin/abamectin is a mixture of two homologs,
Macrocyclic lactones (MLs) consist of several com-
i.e., not less than 80% of 22,23-dihydroavermectin B 1a and
pounds (doramectin, eprinomectin, ivermectin, milbemy-
not more than 20% of 22,23-dihydroavermectin B 1b .The
cin, moxidectin, and selamectin) that are commonly used
B 1a and B 1b components differ from each other by a single
as insecticides, acaricides, and nematicides in various
methylene group, have very similar biological and toxico-
animal species. Chemical structures of these MLs are
logical properties, and can, for all practical purposes, be
shown in Figs. 43.1 43.6. Ivermectin, a semisynthetic considered equipotent (Campbell, 1989). The mixture is
ML, was the first to be obtained from Streptomyces
sold commercially as abamectin. It is a drug of choice
avermitilis. Ivermectin/abamectin is a mixture of
because of its broad spectrum nematicidal, insecticidal, and
two homologs, ivermectin B 1a and ivermectin B 1b
acaricidal properties, and it has been approved for prophy-
(Fig. 43.1). It was introduced to the market in 1981 as a
lactic use against heartworm (D. immitis) infection in dogs.
potent antiparasitic animal health drug. It has been found
Ivermectin is utilized at relatively low dosages. It is
to be effective against virtually all external and internal
effective against a wide range of helminths in sheep and
parasites thus far tested, except for trematodes and ces-
cattle in a single oral or parenteral dose of 0.1 mg/kg body
todes. Ivermectin is approved at a very low dosage for
weight (Egerton et al., 1979). Ivermectin is approved for
the control of parasites in many animal species (cattle,
use in sheep, goats, swine, beef cattle, horses, and reindeer
sheep, swine, horse, cat, and dog), but in many countries
at dosages ranging from 0.2 to 0.5 mg/kg orally, topically,
it is not approved for use in lactating cows, sheep, and
or subcutaneously (Bimectin, Duocare, Ecomectin, Equell,
goats. In agriculture, ivermectin is used for its miticidal,
Eqvalan, Iver-On, Iversol, Ivomec, Noromectin, Primectin,
insecticidal, and acaricidal activities.
Privermectin, Phoenectin, SparMectin-E, Ziimecterin).
Although ML poisoning has been reported in many
The tolerances for American bison, beef cattle, reindeer,
animal species due to inadvertent overdose or misuse
swine, and sheep are 15, 15, 15, 20 and 30 ppb of dihy-
(Godber et al., 1995; Haldrick et al., 1995), a major con-
droavermecin B 1a , respectively, for liver, and 20 ppb
cern of ML toxicosis is in individuals of certain dog
(swine) and 650 ppb (cattle) for muscle (CFR, 1998).
breeds, such as collies (Paul et al., 1987), which are very
Ivermectin is not approved for lactating animals whose
sensitive to this class of drug due to genetic defects in the
milk will enter the food chain. Ivermectin is approved for
blood brain barrier (BBB). To date, over 11 dog breeds
use in ranch-raised foxes at a dosage of 0.2 mg/kg subcu-
(Houston et al., 1987; Geyer et al., 2007; Mosher and
taneously for control of ear mites (Ivomec). Ivermectin is
Court, 2010), Murray Grey cattle (Seaman et al., 1987),
approved in cats as a heartworm preventative, and for con-
and young animals have also been reported to be more
trol of internal helminths at a monthly dosage of 24 μg/kg
sensitive to ML toxicosis. This chapter describes the toxic-
(Heartgard), and as an otic preparation to control ear mites
ity of ML endectocides in animals.
(Acarexx). In dogs, ivermectin is approved for prevention
of heartworms, and control of internal helminths at an oral
dosage of 6 μg/kg (Heartgard, Advantage, Iverhart, Tri-
BACKGROUND Heart).
Selamectin, a novel semisynthetic avermectin, is mar-
Currently, there are many MLs available on the market
keted as Revolution (Pfizer). Revolution is a topical anti-
for their wide applications as insecticides, nematicides,
parasitic preparation recommended for use in dogs and
and acaricides. Ivermectin and its derivatives are most
Veterinary Toxicology. DOI: http://dx.doi.org/10.1016/B978-0-12-811410-0.00043-X
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