Safety of selamectin in dogs

Novotny, Mark J.; Krautmann, M. J.; Ehrhart, J; Godin, Chantal; Evans, Everett Idris; McCall, John W.; Sun, Fangshi; Rowan, T.G.; Jernigan, A.D

doi:10.1016/s0304-4017(00)00306-x

Cited by 57 publications

(34 citation statements)

References 15 publications

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“…Selamectin was the first topically-administered endectocide approved for companion animals with a good safety profile in Collies within a defined dose range (Bishop et al 2000;Novotny et al 2000). Following oral and topical administration to avermectin-sensitive Collies, it was reported to be well tolerated at doses above those recommended for therapeutic use (Novotny et al 2000), although there was no confirmatory genetic test available at that time.…”

Section: Introductionmentioning

confidence: 98%

“…Following oral and topical administration to avermectin-sensitive Collies, it was reported to be well tolerated at doses above those recommended for therapeutic use (Novotny et al 2000), although there was no confirmatory genetic test available at that time. Results from our previous studies suggested that selamectin is also a potent P-gp substrate and inhibitor and that ivermectin and selamectin are both transported by a similarly polarized P-gp-sensitive mechanism across Caco-2 monolayers and canine peripheral blood lymphocytes (Griffin et al 2005).…”

Section: Introductionmentioning

confidence: 98%

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Avermectin transepithelial transport in MDR1- and MRP-transfected canine kidney monolayers

Brayden

Griffin

2007

Vet Res Commun

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Fluxes of the anti-parasitic agents, [(3)H]-ivermectin, [(3)H]-selamectin and [(3)H]-moxidectin were studied across non-transfected and transfected canine kidney epithelial monolayers, MDCK II/wt, MDCK II-MDR1, MDCK II-MRP1 and MDCK II-MRP2. All four lines surprisingly expressed significant levels of P-glycoprotein (P-gp), coded for by MDR1, but MDCK II-MDR1 expressed increased levels compared to the other lines. MDCK II-MRP1 and MDCK II-MRP2 expressed increased levels of MRP1 and MRP2 respectively. Fluxes of [(3)H]-ivermectin, [(3)H]-selamectin, [(3)H]-moxidectin, and the P-gp substrates, rhodamine-123 and DiOC(2), were polarized in the basolateral-to-apical (secretory) direction across the four lines. Selected MRP inhibitors used in relevant pharmacological concentrations did not block the secretory fluxes of either [(3)H]-ivermectin or [(3)H]-selamectin in either the non-transfected or MRP-transfected lines. In contrast, secretory fluxes of ivermectin and selamectin were inhibited in all four lines by the P-gp inhibitor, verapamil. These data confirm that ivermectin and selamectin are substrates for P-gp in four additional cell lines, but suggest that they are not significant substrates for MRP1 or MRP2 where there is background expression of P-gp. Since this pattern of expression also pertains on the blood-brain barrier, it is unlikely that MRP1 and MRP2 play a significant role in ivermectin and selamectin blood: brain distribution in vivo.

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Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 98%

Avermectin transepithelial transport in MDR1- and MRP-transfected canine kidney monolayers

Brayden

Griffin

2007

Vet Res Commun

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“…In contrast, other macrocyclic lactones, such as selamectin, moxidectin and milbemycin oxime, claim to be safer in the treatment of MDR1(-/-) dogs and seem to have a lower neurotoxicological potential. Milbemycin oxime and selamectin only showed mild neurological toxicity in MDR1 mutant dogs at oral doses of ≥ 5 mg/kg and >15 mg/kg, respectively [84,90,91]. Moxidectin seems to be intermediate in this respect and induced mild neurotoxicosis in MDR1 mutant dogs at doses of ≥ 400-1000 µg/kg [58,92].…”

Section: Treatment Of Mdr1 Mutant Dogs With Macrocyclic Lactonesmentioning

confidence: 99%

Treatment of MDR1 Mutant Dogs with Macrocyclic Lactones

Geyer

Janko²

2012

CPB

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P-glycoprotein, encoded by the multidrug resistance gene MDR1, is an ATP-driven drug efflux pump which is highly expressed at the blood-brain barrier of vertebrates. Drug efflux of macrocyclic lactones by P-glycoprotein is highly relevant for the therapeutic safety of macrocyclic lactones, as thereby GABA-gated chloride channels, which are confined to the central nervous system in vertebrates, are protected from high drug concentrations that otherwise would induce neurological toxicity. A 4-bp deletion mutation exists in the MDR1 gene of many dog breeds such as the Collie and the Australian Shepherd, which results in the expression of a non-functional P-glycoprotein and is associated with multiple drug sensitivity. Accordingly, dogs with homozygous MDR1 mutation are in general prone to neurotoxicity by macrocyclic lactones due to their increased brain penetration. Nevertheless, treatment of these dogs with macrocyclic lactones does not inevitably result in neurological symptoms, since, the safety of treatment highly depends on the treatment indication, dosage, route of application, and the individual compound used as outlined in this review. Whereas all available macrocyclic lactones can safely be administered to MDR1 mutant dogs at doses usually used for heartworm prevention, these dogs will experience neurological toxicity following a high dose regimen which is common for mange treatment in dogs. Here, we review and discuss the neurotoxicological potential of different macrocyclic lactones as well as their treatment options in MDR1 mutant dogs.

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“…Selamectin (SEL), a new macrocyclic lactone anthelmintic, is a novel avermectin, which has a unique combination of safety in most mammals and is potent against both external and internal parasites of dogs and cats (Novotny et al 2000;Wang et al 2008a). SEL has been introduced by the Chinese Ministry of Agriculture and marketed since 2006 (Wang et al 2008b).…”

Section: Introductionmentioning

confidence: 99%

Haemaphysalis concinna (Acari: Ixodida): persistent efficacy of selamectin in Angora rabbits under laboratory conditions

et al. 2011

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In the present study, the persistent efficacy of selamectin (SEL) in Angora rabbits infested with Haemaphysalis concinna was observed. SEL (6 mg/kg) was administered to rabbits with a single topical application. Eighteen Angora rabbits were randomly allocated to three groups of six rabbits each. At days 1, 8, 15, 22, and 29 following SEL administration, rabbits were inoculated with larval, nymphal, and adult ticks and were then observed for a period of 7 days. The cumulative reduction rates at days 1, 8, 15, 22, and 29 for dead ticks were 100%, 100%, 100%, 95.0%, and 76.7%, respectively, for larvae; 100%, 100%, 100%, 85.0%, and 65.0%, respectively, for nymphs; and 100%, 95.0%, 85.0%, 60.0%, and 45.0%, respectively, for adults. The cumulative reduction rates for larvae in untreated Angora rabbits (controls) were 3.3%, 1.7%, 3.3%, 5.0%, and 5.0%, respectively. There was no reduction of nymphs and adults in untreated Angora rabbits (controls). The reduction rates for larvae, nymphs, and adults were significantly higher for Angora rabbits inoculated with SEL than the controls (P < 0.001).

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Safety of selamectin in dogs

Cited by 57 publications

References 15 publications

Avermectin transepithelial transport in MDR1- and MRP-transfected canine kidney monolayers

Avermectin transepithelial transport in MDR1- and MRP-transfected canine kidney monolayers

Treatment of MDR1 Mutant Dogs with Macrocyclic Lactones

Haemaphysalis concinna (Acari: Ixodida): persistent efficacy of selamectin in Angora rabbits under laboratory conditions

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