Safety of Simparica Trio (sarolaner, pyrantel, moxidectin) in heartworm-infected dogs.

Background: Assessment of the safety of heartworm preventatives in dogs with pre-existing patent heartworm (Dirofilaria immitis) infections is necessary because rapid adult worm and microfilarial death can lead to severe clinical complications, including thromboembolism and anaphylactic shock in dogs. The aim of this study was to determine the clinical safety of Simparica Trio (sarolaner, pyrantel, moxidectin) in heartworm-infected dogs and the degree of microfilaricidal and adulticidal activity of three consecutive monthly treatments of Simparica Trio.

Methods: Twenty-four laboratory Beagle dogs were implanted with 10 male and 10 female D.

Insecticidal activity of Simparica and Simparica Trio against Aedes aegypti in dogs.

Background: Aedes aegypti is one of the main species responsible for the transmission of mosquito-borne pathogens worldwide. The isoxazoline Sarolaner has excellent efficacy as an acaricide against ticks and mites and as an insecticide against fleas, and potential efficacy against other insects.

Methods: In each of two laboratory studies, 24 dogs were randomly allocated (n = 8/group) to an untreated control group, a Simparica-treated group (at the minimum dose of 2.

Preventive efficacy of six monthly oral doses of Simparica Trio, Heartgard Plus, and Interceptor Plus against a macrocyclic lactone-resistant strain (ZoeLA) of heartworm (Dirofilaria immitis) in dogs.

Background: Administration of four to six consecutive monthly doses of 24 µg/kg moxidectin alone shows high effectiveness in preventing the maturation of macrocyclic lactone (ML)-resistant heartworm strains, Dirofilaria immitis JYD-34 and ZoeLA. This laboratory study evaluated the efficacy of six consecutive monthly oral doses of Simparica Trio (moxidectin/sarolaner/pyrantel) compared to six monthly doses of either Heartgard Plus (ivermectin/pyrantel) or Interceptor Plus (milbemycin oxime/praziquantel) against ML-resistant D. immitis ZoeLA strain.

Moxidectin: heartworm disease prevention in dogs in the face of emerging macrocyclic lactone resistance.

Heartworm (Dirofilaria immitis) disease continues to increase and spread, remaining one of the most important and pathogenic parasitic diseases of dogs, despite the regular use of macrocyclic lactones (MLs) in preventive products. Dogs harboring strains of D. immitis resistant to MLs, the only drug class available for heartworm prevention in the United States, have been documented and proven.

Cryogenic preservation of Dirofilaria immitis microfilariae, reactivation and completion of the life-cycle in the mosquito and vertebrate hosts.

Background: The cryopreservation of filarial nematodes has been studied for nearly 70 years. Largely, these studies examined the effectiveness of cryopreservation methods by using the post-thaw survival of microfilariae (mf) and the development to third-stage larvae (L3s) following inoculation into a competent insect vector. Only one study reported complete reestablishment of a filarial nematode (Brugia malayi) life-cycle in a competent vertebrate host from cryopreserved stock.

Comparative preventive efficacy of ProHeart 12, Heartgard Plus and Interceptor Plus against a macrocyclic lactone-resistant strain (JYD-34) of heartworm (Dirofilaria immitis) in dogs.

Background: The current studies compared ProHeart 12, Heartgard Plus and Interceptor Plus for preventive efficacy against JYD-34, a macrocyclic lactone (ML)-resistant strain of Dirofilaria immitis in dogs.

Methods: In two studies, each using 24 adult beagles, dogs were allocated to four treatment groups (n = 6): placebo-treated control; ProHeart 12 as per label (0.5 mg/kg moxidectin); Heartgard Plus (HGP) as per label (minimum 6 µg/kg ivermectin); and Interceptor Plus (INP) as per label (minimum 0.

Preventive efficacy of four or six monthly oral doses of 24 µg/kg moxidectin compared to six monthly doses of Heartgard® Plus or Interceptor® Plus against macrocyclic lactone-resistant heartworm (Dirofilaria immitis) strains in dogs.

Background: Recent reports indicated that increasing the monthly oral dosage and the number of consecutive monthly doses of moxidectin improved the efficacy against macrocyclic lactone (ML)-resistant Dirofilaria immitis. The two laboratory studies reported here evaluated the efficacy of four or six monthly oral doses of 24 µg/kg moxidectin compared to six monthly doses of either Heartgard® Plus (ivermectin/pyrantel) or Interceptor® Plus (milbemycin oxime/praziquantel) against ML-resistant D. immitis strains.

The efficacy of a topical formulation of selamectin plus sarolaner in preventing the development of a macrocyclic lactone-resistant strain of Dirofilaria immitis in cats.

Revolution®/Stronghold® Plus, a topical endectocide incorporating 6 mg/kg selamectin plus 1 mg/kg sarolaner, is approved for use in cats to prevent heartworm disease. The efficacy of selamectin has not previously been evaluated against any macrocyclic lactone (ML)-resistant heartworm strains in cats for prevention of heartworm disease. In this study, an experimental combination formulation of selamectin (6 mg/kg) plus sarolaner (2 mg/kg) was assessed for preventing the development of a ML-resistant strain of Dirofilaria immitis in cats.

Laboratory and field studies to investigate the efficacy of a novel, orally administered combination product containing moxidectin, sarolaner and pyrantel for the prevention of heartworm disease (Dirofilaria immitis) in dogs.

Background: Dirofilaria immitis is a filarial parasite of dogs that can cause serious or fatal cardiopulmonary disease. Three studies were conducted to evaluate the efficacy and safety of monthly treatment with moxidectin in a chewable tablet product in combination with sarolaner and pyrantel to prevent heartworm disease in dogs after experimental challenge and in a clinical field study in the USA.

Methods: In two laboratory studies, dogs (8 per group) that had been inoculated 30 days prior with 50 third-stage D.

Preventive efficacy of oral moxidectin at various doses and dosage regimens against macrocyclic lactone-resistant heartworm (Dirofilaria immitis) strains in dogs.

Background: Moxidectin has previously shown limited efficacy (≤ 44.4%) against confirmed macrocyclic lactone (ML)-resistant Dirofilaria immitis strains at 3 µg/kg after single and multiple oral dosages. Three studies were conducted to evaluate higher oral moxidectin doses for efficacy against confirmed ML-resistant D.

ProHeart® 12, a moxidectin extended-release injectable formulation for prevention of heartworm (Dirofilaria immitis) disease in dogs in the USA for 12 months.

Background: The efficacy of an extended-release injectable moxidectin (0.5 mg/kg) suspension (ProHeart® 12) (PH 12) in preventing the development of Dirofilaria immitis in dogs for 12 months was investigated in laboratory and field studies in the USA.

Methods: In each of two laboratory studies, 20 dogs ≥ 12 months of age were randomly allocated to receive a subcutaneous injection of saline or PH 12 on Day 0 and were then inoculated with 50 D.

The efficacy of a novel topical formulation of selamectin plus sarolaner (Revolution Plus/Stronghold Plus) in preventing the development of Dirofilaria immitis in cats.

Three controlled studies were conducted to investigate the efficacy of selamectin plus sarolaner (Revolution Plus/Stronghold Plus) in preventing feline heartworm disease in cats. In all studies, cats were inoculated with 100 Dirofilaria immitis third stage larvae on Day -30. In the first study, cats were treated with selamectin plus sarolaner as a single dose on Day 0 or as three consecutive monthly doses on Days 0, 28 and 56.

Evaluation of the efficacy of ProHeart 6 (moxidectin) against a resistant isolate of Dirofilaria immitis (JYD-34) in dogs.

Background: In a previous study, it was demonstrated that ProHeart 6 (PH6) (moxidectin, Zoetis) provided only about 20% efficacy in a small six-dog study against a macrocyclic lactone -resistant Dirofilaria immitis isolate (Jd2009-2) when dogs were inoculated with infective third-stage larvae (L3) at the end of the dosing period (ie, 180 days post treatment). The objective of the current study was to determine the prophylactic efficacy of a moxidectin sustained-release formulation (PH6) against a confirmed macrocyclic lactone-resistant isolate of D. immitis (JYD-34) in dogs when administered by subcutaneous injection at the labeled dose of 0.

Genetic profiles of ten Dirofilaria immitis isolates susceptible or resistant to macrocyclic lactone heartworm preventives.

Background: For dogs and cats, chemoprophylaxis with macrocyclic lactone (ML) preventives for heartworm disease is widely used in the United States and other countries. Since 2005, cases of loss of efficacy (LOE) of heartworm preventives have been reported in the U.S.

Microfilarial reduction following ProHeart® 6 and ProHeart® SR-12 treatment in dogs experimentally inoculated with a resistant isolate of Dirofilaria immitis.

Background: Emerging resistance of heartworms (Dirofilaria immitis) to macrocyclic lactone (ML) preventives is an increasing concern for veterinarians, pet owners and animal health companies that supply heartworm preventives, with recent reports of resistant isolates identified from the Mississippi Delta region of the United States. Products that are effective in eliminating microfilariae (MF) in dogs harboring resistant heartworm infections could be important in reducing the spread of heartworm resistance. The current study was conducted to investigate the potential for ProHeart® 6 (PH 6; Zoetis) and ProHeart® SR-12 (PH 12; Zoetis) to reduce MF in dogs experimentally inoculated with an isolate of D.

Efficacy of oral moxidectin against susceptible and resistant isolates of Dirofilaria immitis in dogs.

Background: Monthly topical and sustained-release injectable formulations of moxidectin are currently marketed; however, an oral formulation, while approved at a dose of 3 μg/kg, is not currently marketed in the United States. Although resistance of heartworms to all macrocyclic lactone (ML) heartworm preventives (ivermectin, milbemycin, selamectin and moxidectin) has been demonstrated, to date no data have been reported on the effectiveness of oral moxidectin against recent isolates of Dirofilaria immitis.

Methods: A total of nine studies were conducted to determine the efficacy of moxidectin against a range of older and recently sourced heartworm isolates.

Efficacy of a new spot-on formulation of selamectin plus sarolaner against Ancylostoma tubaeforme and Toxocara cati in cats.

The efficacy of a new spot-on formulation of selamectin plus sarolaner for cats was evaluated against induced infections with Ancylostoma tubaeforme (hookworm) and Toxocara cati (roundworm). Five laboratory studies were conducted using adult, purpose-bred cats. Four of the studies were designed to evaluate efficacy of the combination against A.

Dirofilaria immitis exhibits sex- and stage-specific differences in excretory/secretory miRNA and protein profiles.

The canine heartworm Dirofilaria immitis releases excretory/secretory molecules into its host and in culture. We report analyses of the types, amounts and stage-dependence of microRNAs and proteins found in D. immitis culture media recovered after incubating 800,000 microfilariae for 6days, 500L and 500L for 7days, as well as 40 adult females and 40 adult males for 48h, all separately.

Discovery of sarolaner: A novel, orally administered, broad-spectrum, isoxazoline ectoparasiticide for dogs.

The novel isoxazoline ectoparasiticide, sarolaner, was identified during a lead optimization program for an orally-active compound with efficacy against fleas and ticks on dogs. The aim of the discovery program was to identify a novel isoxazoline specifically for use in companion animals, beginning with de novo synthesis in the Zoetis research laboratories. The sarolaner molecule has unique structural features important for its potency and pharmacokinetic (PK) properties, including spiroazetidine and sulfone moieties.

Determination of the effective dose of a novel oral formulation of sarolaner (Simparica™) for the treatment and month-long control of fleas and ticks on dogs.

Three laboratory studies were conducted to determine the appropriate dose of sarolaner, a novel isoxazoline, for the treatment and month-long control of infestations of fleas and ticks on dogs. In the first study, dogs were treated orally with sarolaner suspension formulations at 1.25, 2.

Design and synthesis of sarolaner, a novel, once-a-month, oral isoxazoline for the control of fleas and ticks on dogs.

Over the last decade, the isoxazoline motif has become the intense focus of crop protection and animal health companies in their search for novel pesticides and ectoparasiticides. Herein we report the discovery of sarolaner, a proprietary, optimized-for-animal health use isoxazoline, for once-a-month oral treatment of flea and tick infestation on dogs.

The discovery of isoxazoline oxime ethers as a new class of ectoparasiticides for the control of Haematobia irritans (horn fly) in cattle.

Haematobia irritans (horn fly) infestation in cattle is responsible for over a billion dollars a year in global economic loss due to decreased milk production and lower feed conversion. There is significant need for new insecticidal agents since current treatments such as organophosphates and pyrethroids suffer from field resistance. Isoxazoline oxime ethers represent a new class of γ-aminobutyric acid (GABA) receptor channel blockers which show good activity (LD(90) = 1.

Efficacy of selamectin in the treatment and control of clinical signs of flea allergy dermatitis in dogs and cats experimentally infested with fleas.

Objective: To determine whether treatment with selamectin would reduce clinical signs of flea allergy dermatitis (FAD) in dogs and cats housed in flea-infested environments.

Design: Randomized controlled trial.

Animals: 22 dogs and 17 cats confirmed to have FAD.

Efficacy and safety of topical administration of selamectin for treatment of ear mite infestation in rabbits.

Objective: To evaluate the efficacy and safety of topical administration of selamectin in rabbits naturally infested with Psoroptes cuniculi.

Design: Randomized controlled trial.

Animals: 48 mixed-breed domestic rabbits with active P.