Acaricidal Properties Research Articles

Establishment of antitick efficacy of a phytoformulation prepared from Annona squamosa leaf extracts for the management of acaricide resistant tick infestations on cattle

To combat the problem of acaricide resistance in ticks, efforts have been made to develop eco-friendly herbal acaricides which are safe for animal use with no possibilities of evoking environment and residual toxicity. In the present study, the acaricidal properties of a commonly available plant, Annona squamosa have been established to develop a novel antitick phytoformulation using leaf extract, suitable solvents and emulsifier for managing resistant tick infestations in animals. The quality control of the safe and stable phytoformulation using Rutin as a major constituent was maintained by HPTLC profiling.Several phytformulations (A-E) were prepared and formulation ‘C’ is identifried as the most effective showing 52.5–75% antitick activity against in vitro treated resistant strains of R. microplus (IVRI-IV and V) with 33.8–40.2% inhibition of oviposition while 65–85% mortality against multiacaricide resistant field populations. The phytoformulation provided 70.4% efficacy after first larval challenge in experimentally infested animals. The field efficacy of the formulation in different multilocational field trials was 68.53–77.8%. The detail antitick efficacy of the formulation along with safety and stability are explained as a component of antitck technology to manage resistant tick problem in livestock.

Mode of action and toxicological effects of the sesquiterpenoid, nootkatone, in insects

Nootkatone, a sesquiterpenoid isolated from Alaskan yellow cedar (Cupressus nootkatensis), is known to possess insect repellent and acaricidal properties and has recently been registered for commercial use by the Environmental Protection Agency. Previous studies failed to elucidate the mechanism of action of nootkatone, but we found a molecular overlay of picrotoxinin and nootkatone indicated a high degree of structural and electrostatic similarity. We therefore tested the hypothesis that nootkatone was a GABA-gated chloride channel antagonist, similar to picrotoxinin. The KD50 and LD50 of nootkatone on the insecticide-susceptible strain of Drosophila melanogaster (CSOR) showed resistance ratios of 8 and 11, respectively, compared to the cyclodiene-resistant strain of RDL1675, indicating significant cross-resistance. Nootkatone reversed GABA-mediated block of the larval CSOR central nervous system; nerve firing of 78 ± 17% of baseline in the CSOR strain was significantly different from 24 ± 11% of baseline firing in the RDL1675 strain (p = 0.035). This finding indicated that the resistance was expressed within the nervous system. Patch clamp recordings on D. melanogaster central neurons mirrored extracellular recordings where nootkatone inhibited GABA-stimulated currents by 44 ± 9% at 100 μM, whereas chloride current was inhibited 4.5-fold less at 100 μM in RDL1675. Taken together, these data suggest nootkatone toxicity in D. melanogaster is mediated through GABA receptor antagonism.

Phytochemistry, anti-tick, repellency and anti-cholinesterase activities of Cupressus sempervirens L. and Mentha pulegium L. combinations against Hyalomma scupense (Acari: Ixodidae)

The adulticidal, larvicidal, and repellent effects of Cupressus sempervirens, Mentha pulegium, and their combination (C. sempervirens and M. pulegium) against Hyalomma scupense were investigated, as well as their putative mode of action. The evaluation on H. scupense was performed with the adult immersion test at concentrations ranging from 2.5–20 mg/mL and the larval packet test from 0.625 to 20 mg/mlL. The same concentrations were used for combined oils. Essential oils were obtained using hydrodistillation and then analyzed using GC–MS. The following major components were identified: α-pinene (56.89 %) and δ-3-Carene (15.61 %) for C. sempervirens, while pulegone (70.50 %) and cis-Menthone (18.26 %) for M. pulegium. At 20 mg/mL concentration, C. sempervirens had (94.40 %) acaricide action and inhibited the egg from hatching, however at 10 mg/mL, it had 100 % larvicidal activity. Adulticidal and larvicidal activities of M. pulegium oil reached to 87.19 % and 81.02 % respectively, at 20 mg/mL concentration. The highest acaricidal property against H. scupense was exhibited by combination oils with minimum LC50 values of 1.76 mg/mL on adultes and 0.60 mg/mL on larvae. The repellent activities were 100, 95.80 and 100 %, at the 20 mg/mL concentration used in 6 h, for C. sempervirens, M. pulegium and mixture oil respectively. Our findings revealed that the mixture of C. sempervirens and M. pulegium, at the ratio 1:1 (v: v) of each oil, showed high synergistic effect (SF > 1) and the use of combination oil (C. sempervirens 50 %: M. pulegium 50 %) is more toxic against H.scupense. Furthermore, the volatile oils examined revealed significant inhibition of H.scupense acetylcholinesterase activity AChE.Based on the findings of the present framework, these essential oils have the potential to be applied as substitute for synthetic acaricides in the management of H.scupense bovine ticks.

Synthesis, Reactivity, and Applications of 4-Amino-3-Thioxo/Hydrazino-6-Substituted-1,2,4-Triazin-5-Ones and Their Derivatives: A Review

Triazine derivatives have attracted increasing attention due to their diverse applications in medicinal chemistry. They have been reported to be remarkably effective compounds regarding their bioactivities. Therefore, the synthesis and identification of new triazine-derived compounds are of interest for their therapeutic effects. Various approaches have been developed to synthesize triazine derivatives. In this review, a considerable number of studies on the synthesis of 1,2,4-triazine derivatives are investigated with 4-amino-3-thioxo-6-substituted-1,2,4-triazin-ones and 4-amino-3-hydrazino-6-substituted-1,2,4-triazin-5-ones as starting materials. Different types of chemical reactions have been applied to the efficient synthesis of 3-thioxo/hydrazino-6-substituted-1,2,4-triazin-5-ones, such as alkylation, acylation, aroylation, elimination, substitution, acidic/basic hydrolysis, oxidation, cyclocondensation, cycloaddition, phosphorylation, and complexation reactions. Interestingly, a set of compounds is identified to possess various biological activities, such as anticancer antibacterial, antifungal, acaricidal, and molluscicidal properties. Also, some 4-amino-3-thioxo-6-substituted-1,2,4-triazin-5-one derivatives are found to form metal complexes, be used as inhibitor probes for mild steel corrosion, prepare a selective sensor for the determination of gadolinium (III) ions in the soil and sediment samples, and demonstrate antibacterial activities. Finally, 4-amino-3-hydrazino-6-methyl-1,2,4-triazin-5-one was used as an ionophore to develop a chromium (III) ion-selective sensor beside the formation of silver complexes.

Efficacy of a topical product combining esafoxolaner, eprinomectin and praziquantel against bedbug (Cimex lectularius) experimental infestations in cats.

Bedbugs (Cimex lectularius) are a persistent nuisance pest for humans and their home environment, and may also opportunistically feed on other mammals, including household pets like dogs and cats. NexGard® Combo is a topical endectoparasiticide product for cats combining esafoxolaner, an isoxazoline compound with insecticidal and acaricidal properties, the nematocide eprinomectin and the cestocide praziquantel. The insecticidal efficacy of this product was evaluated in cats experimentally infested with C. lectularius in a blinded, negative controlled and randomized study. Two groups of 7 cats were formed: an untreated control group, and a NexGard® Combo group treated once on Day 0at the label dose. Cats were then challenged weekly, each with twenty unfed adult C. lectularius, on Days 1, 7, 14, 21 and 28. After close contact with the cat's skin for 15min, live fed C. lectularius were collected and incubated for 96h. The weekly efficacy evaluations were based on a comparison of the number of surviving bedbugs in the control and the treated group after 48, 72 and 96h of incubation. The model was demonstrated to be robust as in the control group the average feeding rate after the 15-minute challenge was 94%, and as 96% of incubated bed bugs were alive after 96 hours of incubation. Significant live bedbug reductions were demonstrated in the Nexgard® Combo treated group: after 96h of incubation, the reductions ranged from 80.6 to 88.0% during the Day 1 to Day 21 period, and dropped to 58% at Day 28.

Bioefficacy of newer insecticides against sucking pests; jassid, whitefly and mite on Brinjal (Solanum melongena L.)

The present investigation was carried out at the Research Farm of Department of Agricultural Entomology, VNMKV, Parbhani during kharif 2018–19 to evaluate the efficacy of insecticides against sucking pests of brinjal. Seven insecticidal treatments cyantraniliprole OD, ffnpropathrin EC, flubendiamide SC, cartaphydrochloride SG, emamectin benzoate SG, λ-cyhalothrin EC and chlorantraniliprole SC were evaluated. Three sprays of each treatment at the interval of 15 days, starting with beginning of pest infestation, were given during the experiment. Cyantraniliprole 10.26% OD was found to be superior over the other insecticides. It recorded the lowest number of jassids and whiteflies, which was on par with the remaining treatments. Though the insecticides are not acaricides, but they showed a significant reduction in mite population over the untreated control plot. Fenpropathrin 30% EC was found effective against mites. This finding will be useful to identify the chemical combinations showing both insecticidal as well as acaricidal properties.

The effectiveness of acaricidic drugs based on herbal raw material

Limitation the number of ixodes ticks is one of the most important tasks of modern science and requires the search for new, highly effective and environmentally hazardous acaricides, so our experiment was aimed at identifying acaricidal properties of essential oils and their individual active components in the population of ixodes ticks in Zaporizhzhia region. The study of acaricidal properties of essential oils was performed in the laboratory conditions. Tampons with wool were soaked in various concentrations of 0.5%, 1%, 3%, 5% and 10% aqueous emulsion of essential oils such as Caryophyllus floris aetheroleum and Limonis aetheroleum, and essential oils of Thymus serpyllum L., Рinus sylvestris L., Salvia officinalis L., Mentha x piperita L. and Eucalyptus viminalis Labill. The essential oils had a significant effect on the lifespan of adult ticks. The results showed the acaricidal effect of Thymus serpyllum essential oils. When searching the acaricidal and repellent properties of individual essential oils components thymole, menthol and citral showed the high activity as acaricides. In the same time, eugenol and borneol proved the effectiveness as repellent. Our research schowed that essential oils are promising as alternative methods of controlling the number of Ixodes ticks in areas where there are conditions for infection with tick infections.

Acaricidal properties of 5-methylfurfural identified from Valeriana fauriei and its structural analogues against synanthropic mites and Asian longhorned tick with color alterations

Acaricidal activities and color alterations of 5-methylfurfural derived from Valeriana fauriei essential oil and its structural analogues against Dermatophagoides farinae, D. pteronyssinus, Haemaphysalis longicornis and Tyrophagus putrescentiae were evaluated in the present study. Based on the LD50 values of 5-methylfurfural and its analogues, 4,5-dimethylfurfural showed the highest acaricidal activity (LD50; 9.95, 9.91, and 7.12 μg/cm2), followed by 5-methylfurfural (11.87, 11.00, and 8.59 μg/cm2), furfural (12.94, 13.25, and 10.36 μg/cm2), and V. fauriei essential oil (15.15, 13.64, and 10.14 μg/cm2) against D. farinae, D. pteronyssinus and T. putrescentiae, respectively. However, all tested compounds did not show the acaricidal activities against H. longicornis. Interestingly, the color alterations of the mites and ticks were observed by furfural, 5-methylfurfural, and 4,5-dimethylfurfural from colorless to red brown during the acaricidal experiments. Furthermore, 4,5-dimethylfurfural which exhibited the highest acaricidal activity was formulated as nanoemulsion. The nanoemulsion of 4,5-dimethylfurfural showed higher acaricidal activity than it was emulsified in ethanol. The nanoemulsion was also found to show color changes of the mites and ticks from colorless to red brown. The results suggest that 5-methylfurfural and its analogues could be developed as an effective and easy-to-recognize acaricides to mites and ticks.

Toxicity evaluation and chemical composition of Capsicum frutescens for natural control of Asian blue tick, Rhipicephalus (Boophilus) microplus (Acari: Ixodidae)

BackgroundIndiscriminate use of synthetic acaricides in the management of veterinary parasites has led to environmental pollution, acaricidal resistance and their residues in the animal products. These problems are directly demanded an alternative acaricidal source for the ticks control and that should be cost-effective, eco-friendly and target specific. The current study demonstrated the acaricidal effects of Capsicum frutescens (fruits) against the cattle tick Rhipicephalus (Boophilus) microplus. In adult immersion test, the effects of the treatment on engorged females were assessed by measuring egg mass production, estimated reproductive factor, and % inhibition of reproduction.ResultsMethanol extract was observed the most effective against adults with LC50 617.54 ppm and LC90 1040.41 ppm. The other target extracts (petroleum ether and hexane) were less effective to the engorged females of R. microplus. Chemical analysis of the potent extract was elucidated by Gas Chromatography–Mass Spectrometry analysis and Cis-13-octadecenoic acid was observed as main compound (43.54%). The simultaneous evaluation of the qualitative chemical screening of the methanol extract showed the presence of tannins, saponins, carbohydrates, steroids, terpenoids, flavonoids, and alkaloids.ConclusionThe study concludes that the methanol extract of C. frutescens fruits revealed the significant acaricidal properties and may be used as safe alternative for tick management.

A Review of the Phytochemistry, Ethnobotany, Toxicology, and Pharmacological Potentials of Crescentia cujete L. (Bignoniaceae).

Crescentia cujete is an economical and medicinal plant of wide indigenous uses including hypertension, diarrhea, respiratory ailments, stomach troubles, infertility problems, cancer, and snakebite. Despite these attributes, C. cujete is largely underutilized, notwithstanding the few progresses made to date. Here, we reviewed the available findings on the ethnobotany, phytochemistry, toxicology, and pharmacology, as well as other economic benefits of the plant. The information on the review was gathered from major scientific databases (Google scholar, Scopus, Science Direct, Web of Science, PubMed, Springer, and BioMed Central) using journals, books, and/or chapters, dissertations, and conference proceedings. The review established the antidiabetic, antioxidant, acaricidal, antibacterial, anti-inflammatory, anthelmintic, antivenom, wound healing, neuroprotection, antiangiogenic, and cytotoxic properties from aqueous and organic (particularly ethanol) aerial parts attributed to several secondary metabolites such as flavonoids, alkaloids, saponins, tannins, phenols, cardiac glycosides, phytosterols, reducing sugar, and volatile oils. Economically, the fruit hard outer shell found applications as musical tools, tobacco pipes, bowls, food containers, and bioethanol production. While most of the current studies on C. cujete are mainly from Asia and South America (Philippines, Bangladesh, India, etc.), part of the persistence challenge is lack of comprehensive data on the plant from in vivo pharmacological studies of its already characterized compounds for probable clinical trials toward drug discovery. Consequently, upon this, modern and novel translational studies including the concept of ‘-omics' are suggested for studies aiming to outfit more comprehensive data on its therapeutic profiles against pathological markers of diseases and to fully explore its economic benefits.

Acaricidal and ovicidal properties of Lippia alba essential oil and its chemical constituents against red spider mite, Oligonychus coffeae Nietner (Acari: Tetranychidae) infesting tea crops

The red spider mite, Oligonychus coffeae Nietner (Acari: Tetranychidae), is a prevalent mite pest damages tea crops. The present study evaluated the efficacy of L. alba essential oil against O. coffeae. GC and GC-MS analysis of L. alba essential oil revealed geraniol (52.19%) and neral (34.13%) as major compounds. The L. alba essential oil applied at 1500 ppm exhibited 100% mortality of treated mites 48 h after exposure through fumigant toxicity method, while 99% ovicidal activity of essential oil was achieved at 1000 ppm. Similarly, in fumigant bioassay LC50 value against O. coffeae was 87.75 ppm for geraniol and 103.49 ppm for neral at 72 h after exposure. The findings suggest that L. alba essential oil and its major constituents geraniol and neral could be used as eco-friendly acaricide, and can be incorporated as one of the components in IPM after multi-location field trials.

Identification and efficacy of active metabolites of pomegranate fruit peel aqueous extract against sucking pests of rose and their predators

LC ESI Q-TOF metabolomic profiling of pomegranate (Punica granatum Linn.) fruit peel (PFP) aqueous extract was performed to elucidate the possible metabolites present in the PFP, which could be responsible for its acaricidal property against two-spotted spider mites (Tetranychus urticae). Efficacy of PFP aqueous extract has also been evaluated against aphids (Macrosiphum roseiformis), thrips (Scirthothrips dorsalis) as important sucking pests of ornamental rose and for two generalist predators of these pests viz., Coccinella septumpunctata and Orius insidiosus. Toxicity bioassays PFP at 24 h showed highest value of lethal concentrations LC50 for aphids (876 mg/ml) followed by thrips (57 mg/ml) and the least for spider mites (4.5 mg/ml), which shows its high toxicity for spider mites. UHPLC-QTOF/MS analysis has confirmed of several standard and new compounds including presence of genistein, rutin, 2-hydroxy-5-methylquinone, limonene, quercetin 3-O-glucoside, myricetin, kaempferol and alpha-pinene. Kaempferol, quercetin and myricetin confirmed high toxicity towards all the three pests tested. PFP is a biodegradable eco-friendly source that has a promising role in the management of spider mites on roses.

Acaricidal Efficacy of Jasmine and Lavender Essential Oil or Mustard Fixed Oil against Two-Spotted Spider Mite and Their Impact on Growth and Yield of Eggplants.

Simple SummaryThe two-spotted spider mite (TSSM) represents the highly polyphagous pest worldwide in protected and open field condition results in a serious economic yield loss (50-100%) in severe infestation conditions. The ecological crisis attributable to the extra-application of acaricides has been an issue of concern in modern decades. It is former to estimate that nearly 2.5 million tons of pesticides are utilized in agricultural production yearly and the global injury evoked by pesticides achieves $100 billion yearly. It is therefore hoped that natural oils can offer alternative options to synthesis acaricides and contribute to pesticide resistance. Application of essential oils of lavender and jasmine, as well as mustard fixed oil, is inducing the plant resistance to TSSM as well as and improving plant growth and yield of eggplantsEggplant is repeatedly attacked by numerous pests, particularly two-spotted spider mite (TSSM), which considerably decline plant productivity. Synthetic acaricides are frequently applied for controlling TSSM, resulting in environmental pollution. The utilization of rational novel substances which repel or prevent TSSM establishment represents a sustainable eco-friendly to reduce the utilization of agrochemicals. A greenhouse investigation was done for assessing the bio-acaricidal activity of mustard (Brassica juncea L.) fixed oil (MFO), jasmine (Jasminum grandiflorum L.) essential oil (JEO), or lavender (Lavandula angustifolia L.) essential oil (LEO), and their influences on eggplant growth and productivity. The results demonstrated that JEO represents the most acaricidal properties against TSSM followed by MFO and/or LEO compared to control. Spraying with natural oils significantly improved eggplant growth, i.e., plant height, number of leaves, and branches/plant, in addition to the leaf area and relative leaf dry mass of the 3rd–5th upper leaves. The JEO had the strongest positive effect compared with other oils or control. Additionally, Natural oils application significantly increased photosynthetic pigment, chlorophyll a:b ratio, and nitrogen, phosphorus, potassium, ascorbic acid, and phenols. The application of oils increased yield and its quality. In this study, JEO (2.5 mL/l) is shown to be extremely promising for the progress of new eco-friendly acaricides, improving plant growth and increasing eggplant yield.

Acaricidal efficacy and chemical study of hexane extracts of the leaves of Neoglaziovia variegata (Bromeliaceae) against the tick Rhipicephalus microplus.

The frequent use of acaricides against the tick Rhipicephalus microplus increases the risk of development of resistance. Recent studies have revealed that Neoglaziovia variegata, an indigenous plant species known in Brazil as 'caroá', has a deleterious effect against R. microplus. In the current study, extracts of N. variegata were studied for their possible acaricidal properties. A hexane extract of N. variegata leaves was fractionated in a chromatography column and the fractions were tested in adult tick immersion tests in triplicate using three concentrations (5, 10 and 25mg/ml). All the fractions had harmful effects on the ticks. However, three fractions were more efficaceous. Phytochemical analysis indicated that stigmast-5-en-3-ol and stigmastanol were most abundant; they might be responsible for the acaricidal effects, making them potentially useful as alternative agents to control the tick R. microplus.

Acaricidal Properties of Essential Oils from Moroccan Thyme Against Oriental Red Mite, Eutetranychus Orientalis (Klein) (Acari: Tetranychidae)

Essential oils (EOs) from three species of the Lamiaceae family growing in several areas in Morocco, were evaluated for their acaricidal properties against the oriental red mite, Eutetranychus orientalis (Klein) (Acari: Tetranychidae). In this study, different concentrations of thyme oils including Thymus satureioides Coss., T. maroccanus Ball. and T. atlanticus Ball. EOs were used to assess the adulticidal, larvicidal effect by leaf paint method. In addition, the ovicidal effect was evaluated by the leaf disc sprayer method. The obtained results showed that all the EOs tested induce significant mortality to E. orientalis adult females and larvae, and the mortality was increased with increasing the concentration of EOs. In addition, adult females treated with EOs lay fewer eggs than untreated females. Moreover, the highest ovicidal effect on E. orientalis, was induced by T. maroccanus and the lowest effect was induced by T. satureioides and T. atlanticus, respectively at the lowest concentration. The GC/MS analysis showed that the major compounds of T. satureioides EO were borneol (22.7 %), thymol (18.2 %), p-cymene (17.3 %), and α-pinene (6.7 %). The main compounds of T. atlanticus and T. maroccanus EOs are carvacrol (47.1-65.5 %), p-cymene (7.5-20.7 %) and α-pinene (3.7-5.5 %). The results proved that all EOs tested could be used in the integrated pest management of E. orientalis.

Insecticidal efficacy of some essential oils against adults of Musca domestica L. (Diptera: Muscidae)

Nowadays, the insecticidal and acaricidal properties of plant extracts and essential oils (EOs) have been evaluated as an alternative to chemical means. This study aims to assess the insecticidal efficacy of 20 commercial EOs against the adults of Musca domestica Linnaeus (Diptera: Muscidae) by the contact of insects with the residues of EOs at the bottom of glass cups. The dose effects of seven EOs (i.e. Acorus calamus, Allium sativum, Syzygium aromaticum, Cymbopogon citratus, Juniperus communis, Cedrus atlantica, and Foeniculum vulgare) as well as the time effects of exposure to these EOs on the mortality of flies were analyzed by probit analysis. Permethrin (technical substance) was used as a reference insecticide in the positive control and pure acetone served as the negative control. The insecticidal efficacy of the tested EOs decreased in order (based on their lethal dose (LD)50 values): A. calamus > A. sativum > S. aromaticum ≥ C. citratus > J. communis > C. atlantica > F. vulgare. A. calamus EO was the most effective against flies and very fast acting with negligible reversibility of effect. The EOs of A. sativum and S. aromaticum had a significant time-dependent insecticidal effect. The time for 50% insecticidal effect (knockdown and mortality in total) of the A. sativum EO was the greatest among the seven EOs and seven times more in comparison with the positive control. Present results and literature data suggest that the aforesaid plant products could be promising as contact insecticides against adults M. domestica. The difference in the insecticidal properties of A. calamus and A. sativum EOs observed in the current study display the need for various approaches for their future application as insecticides.

Acaricidal Properties of Herbal Extracts against Deltamethrin Resistant Multi-host Cattle Tick Hyalomma anatolicum

Background: Hyalomma ticks are the major ticks prevalent in Gujarat state which are mainly controlled with chemical acaricides. The control strategies are complicated by emergence of resistance against chemical acaricides. Development of resistance against these acaricides has compelled scientists to explore the acaricidal properties of constituents other than chemicals. Methods: Resistance status of Hyalomma anatolicum collected from Gujarat (India) against deltamethrin was assessed by larval packet test, which revealed level I resistance against deltamethrin. The crude ethanolic extracts of leaves of Cymbopogon citratus, Citrus aurantiifolia, Annona squamosa, Carica papaya and Catharanthus roseus were assessed for their acaricidal activity against larvae of deltamethrin resistant H. anatolicum. The efficacy was assessed by measuring per cent larval mortality and determination of LC50 values. Result: Various ethanolic extracts emanated a concentration dependent increase in larval tick mortality. The highest mortality (93.01 ± 0.35%) was observed with the 100mg/ml concentration of ethanolic extract of leaves of C. aurantiifolia. Overall, C. aurantifolia, A. squamosa and C. citratus were found to have significant acaricidal properties with LC95 values of 1.07x102 mg/ml, 6.09x102 mg/ml and 3.62x103 mg/ml respectively. Results of the present study indicated that these plant extracts have potential to be developed as herbal acaricides.

Efficacy of a novel topical combination of esafoxolaner, eprinomectin and praziquantel against Rhipicephalus sanguineus in cats.

Esafoxolaner is a purified enantiomer of afoxolaner with insecticidal and acaricidal properties. It is combined with eprinomectin and praziquantel in a novel topical endectoparasiticide formulation for cats. The efficacy of this novel formulation was assessed in an experimental study against induced infestation of Rhipicephalus sanguineus ticks. Twenty cats were randomly allocated to either a placebo control group or a treated group in a 1:1 ratio. Infested cats were treated topically once at the minimum recommended dose. The study was designed to assess curative efficacy 48 h after treatment and to test preventive efficacy 48 h after weekly infestations for 2 months. At each weekly infestation, all cats were infested with 25 male and 25 unfed female R. sanguineus ticks. At each tick count, at least 6 in 10 control cats had a retention of 13 (26%) or more live ticks, demonstrating adequate infestation throughout the study. Curative efficacy on existing tick infestation was 90%; preventive efficacy over the following 6 weeks was at least 96%.

Pharmacokinetics of a novel endectoparasiticide topical formulation for cats, combining esafoxolaner, eprinomectin and praziquantel.

Esafoxolaner, a purified enantiomer of afoxolaner with insecticidal and acaricidal properties, is combined with eprinomectin and praziquantel in NexGard® Combo, a novel topical endectoparasiticide formulation for cats. The parasiticide potencies of topical esafoxolaner, eprinomectin and praziquantel, are based on transcutaneous absorption, systemic distribution, and exposure of respective target parasites. For each compound, the pharmacokinetic profile, non-interference, dose linearity/proportionality after one administration, and the accumulation and time to reach a steady state after repeated monthly administrations of the novel formulation, were investigated. After one topical application of NexGard® Combo at the minimum recommended dose, the mean plasma concentration of esafoxolaner immediately reached (and remained at) a level supporting rapid onset and sustained efficacy against ectoparasites for at least 1 month. The mean Cmax, Tmax, T1/2, and the topical bioavailability of esafoxolaner were 130 ng/mL, 7.1 days, 21.7 days and 47.2%, respectively, and the plasma profiles of eprinomectin and praziquantel supported their known endoparasiticide properties. No relevant interference between the three compounds was observed. Dose proportionality was demonstrated for the three compounds over a range of 0.5× to 2× the minimum recommended dose. Steady state after repeated monthly administrations was reached by the second dose for praziquantel and by the fifth dose for esafoxolaner and eprinomectin. Accumulation was limited and drug plasma concentrations were maintained within a safe level.

Efficacy of a novel topical combination of esafoxolaner, eprinomectin and praziquantel against adult cat flea Ctenocephalides felis and flea egg production in cats.

Esafoxolaner, a purified enantiomer of afoxolaner with insecticidal and acaricidal properties, is combined with eprinomectin and praziquantel in NexGard® Combo, a novel topical endectoparasiticide formulation for cats. The efficacy of this novel formulation against adult and immature stages of Ctenocephalides felis fleas was tested in four experimental studies. Two studies were designed to test adulticide efficacy, one to test inhibition of immature stages, and one to test both adulticide efficacy and inhibition of immature stages. In each study, cats were randomly allocated to a placebo control group or to a novel formulation group treated once at the minimum recommended dose. Cats were experimentally infested weekly for one to two months with unfed C. felis originating from North America or Europe. For adulticide efficacy evaluations, live fleas were counted 24 h after treatment and after subsequent weekly infestations. For immature stages, flea eggs were collected and counted weekly for evaluation of egg production inhibition and incubated for larval hatching evaluation. In the three studies testing adult fleas, curative efficacies, 24 h after treatment, were 92.1%, 98.3% and 99.7%; preventive weekly efficacies, 24 h after weekly infestations, remained higher than 95.5% for at least one month. In the two studies testing immature stages, egg production and larval hatching was significantly reduced for at least one month. These studies provide robust evidence of efficacy of the novel formulation against experimental adult flea infestations and for the prevention of environmental contamination by immature flea stages, for at least one month.