Eprinomectin pour-on (EPRINEX® Pour-on, Merial): efficacy against gastrointestinal and pulmonary nematodes and pharmacokinetics in sheep.

BACKGROUND: The anthelmintic efficacy of the 0.5% w/v topical formulation of eprinomectin (EPN), EPRINEX® Pour-on (Merial) when administered at 1 mg/kg body weight was evaluated in sheep in two dose confirmation laboratory studies and one multicenter field study. In addition, the pharmacokinetics of EPN when administered at that dosage to adult sheep was determined. RESULTS: In the two dose confirmation studies, which included 10 sheep each, sheep treated with topical EPN had significantly (p < 0.05) fewer of the following nematodes than the untreated sheep with overall reduction of nematode counts by >99%: adult Dictyocaulus filaria, Haemonchus contortus, Teladorsagia circumcincta(pinnata/trifurcata), Trichostrongylus axei, T. colubriformis, T. vitrinus, Cooperia curticei, Nematodirus battus, Strongyloides papillosus, Chabertia ovina and Oesophagostomum venulosum, and inhibited fourth-stage Teladorsagia larvae. A total of 196 sheep harboring naturally acquired gastrointestinal nematode infections were included in the field efficacy study at two sites each in Germany (48 Merino x Ile de France lambs, 52 adult Merino females) and in Italy (adult male and female Bagnolese, Lacaune, Lacaune x Bagnolese, Bagnolese x Sarda sheep; 48 animals per site). Animals were blocked on pre-treatment body weight and within each block, one animal was randomly assigned to the control (untreated) group and three animals were randomly assigned to be treated with topical EPN. Examination of feces 14 days after treatment demonstrated that, relative to the controls, topical EPN-treated sheep had significantly (p < 0.0001) lower strongylid egg counts. Reduction was ≥97% at each site and 98.6% across all sites. Pharmacokinetics of EPN following single treatment with topical EPN were determined in eight ~4.5 year old female Merino cross sheep based on the analysis of plasma samples which were collected from two hours to 21 days following treatment. The main pharmacokinetic parameters were: Cmax 6.20 ± 1.71 ng/mL, AUClast 48.8 ± 19.2 day*ng/mL, Tmax 3.13 ± 2.99 days and T1/2 6.40 ± 2.95 days. No treatment-related health problems or adverse drug events were observed in any study. CONCLUSION: These studies demonstrated 0.5% w/v EPN administered topically at 1 mg/kg body weight to be highly efficacious against a broad range of ovine gastrointestinal nematodes and D. filaria lungworms and well tolerated by sheep of different ages, breeds, gender and physiological status.

Efficacy against nematode infections and safety of afoxolaner plus milbemycin oxime chewable tablets in domestic dogs under field conditions in Europe.

Afoxolaner (AFX) plus milbemycin oxime (MO) combination chewable tablets (NexGard Spectra®, Merial) were evaluated for safety and efficacy against naturally acquired nematode infections in domestic dogs in a multi-centre, positive control, blinded field study using a randomized block design based on the order of presentation for allocation. In total, 408 dogs confirmed positive for naturally acquired infections of intestinal nematodes by pre-treatment faecal examination were studied in ten countries in Europe (Albania, Austria, Bulgaria, France, Germany, Hungary, Italy, Lithuania, Romania and Slovakia). Pre-treatment faecal examination revealed Toxocara, Toxascaris, hookworm, Trichuris and/or Capillaria nematode infections in 134, 30, 223, 155 and 14 dogs, respectively. Dogs were allocated to one of two treatment groups in a ratio of 1, AFX + MO chewables (≥2.5 mg AFX + ≥0.5 mg MO per kg body weight, according to dose bands; 207 dogs), and 1, MO plus praziquantel (PRZ) chewables (Milbemax®, Novartis; ≥0.5 mg MO + ≥5 mg PRZ per kg body weight, according to the manufacturer's instructions; 201 dogs) and treated once. For evaluation of efficacy based on reduction of faecal nematode egg counts, two faecal samples, one collected prior to treatment and one collected 9 to 21 days after treatment, were examined using modified McMaster techniques. For evaluation of systemic safety, dogs were examined by a veterinarian before treatment administration and at study end, and dog owners observed the health status of their dogs until the end of the study and reported any abnormal observation. For dogs treated with AFX + MO chewables, the efficacy was 99.7, 99.7, 97.2, 99.7 and 99.7 % for Toxocara, Toxascaris, hookworm, Trichuris and Capillaria, respectively; and the efficacy was 99.5, 99.4, 94.3, 99.9 and 98.0 %, respectively, for the MO + PRZ-treated dogs (p ≤ 0.002 for all nematodes and both treatments). For Toxocara, hookworm and Trichuris, non-inferiority analysis demonstrated that the efficacy of AFX + MO chewable tablets was equal to or better than that of MO + PRZ. In spite that both treatments were ≥98 % efficacious against Toxascaris and Capillaria, a hypothesis of non-inferiority for both genera could not be established due to the low number of dogs infected with these parasites. No treatment-related adverse experiences were observed throughout the study. For both treatments, all dogs were given a systemic safety score of 'excellent' apart from one dog in each treatment group which received a score of 'acceptable'. AFX + MO combination chewables were shown to be safe and demonstrated a high level of efficacy when administered once to dogs infected with a broad range of parasitic nematodes under field conditions.

Efficacy of a novel topical combination of esafoxolaner, eprinomectin and praziquantel against Notoedres cati mange in cats.

The therapeutic efficacy against notoedric mange of a topical combination of esafoxolaner, eprinomectin and praziquantel (Nexgard® Combo, Boehringer Ingelheim) was evaluated in a masked, controlled clinical study including 14 cats with natural or induced Notoedres cati infestation. Cats were allocated randomly to two groups of seven cats each, to be administered either mineral oil (placebo control) or NexGard® Combo. Each treatment was administered once as spot-on at 0.12 mL per kg body weight (representing the minimum label dosage of NexGard® Combo, i.e. 1.44 mg esafoxolaner, 0.48 mg eprinomectin, and 10.0 mg praziquantel per kg body weight). Live mites were counted in skin scrapings collected within seven days prior to and 14, 27/28, 42 and 56 days after treatment to calculate the percentage efficacy of NexGard® Combo based on the comparison of mean live mite counts of the two groups. Concurrently, mange lesions and clinical signs were scored to establish a clinical success valuation. No live mites were recovered from any NexGard® Combo-treated cats post-treatment, indicating 100% therapeutic efficacy following a single spot-on administration of the novel antiparasitic combination. The clinical success valuations in the NexGard® Combo-treated cats were 14.3%, 42.8%, 100% and 100% at 14, 27/28, 42 and 56 days after treatment, respectively. No health problems were observed throughout the study.

TITLE: Efficacité d'une nouvelle association topique d'esafoxolaner, d'éprinomectine et de praziquantel contre la gale à Notoedres cati chez le chat. ABSTRACT: L'efficacité thérapeutique contre la gale notoédrique d'une association topique d'esafoxolaner, d'éprinomectine et de praziquantel (Nexgard® Combo, Boehringer Ingelheim) a été évaluée dans une étude clinique contrôlée et masquée portant sur 14 chats atteints d'une infestation naturelle ou induite par Notoedres cati. Les chats ont été répartis au hasard en deux groupes de sept chats chacun, traités soit avec de l'huile minérale (contrôle placebo), soit avec NexGard® Combo. Chaque traitement a été administré en une seule fois à raison de 0,12 mL par kg de poids corporel (représentant la posologie minimale indiquée sur l'étiquette de NexGard® Combo, c'est-à-dire 1,44 mg d'esafoxolaner plus 0,48 mg d'éprinomectine plus 10,0 mg de praziquantel par kg de poids corporel). Les acariens vivants ont été comptés par grattage de peau et recueillis dans les sept jours précédant le traitement et 14, 27/28, 42 et 56 jours après le traitement pour calculer le pourcentage d'efficacité de NexGard® Combo basé sur la comparaison du nombre moyen d'acariens vivants des deux groupes. Parallèlement, les lésions de la gale et les signes cliniques ont été mesurés pour établir une évaluation du succès clinique. Aucun acarien vivant n'a été retrouvé chez les chats traités par NexGard® Combo après le traitement, ce qui indique une efficacité thérapeutique de 100% après une administration ponctuelle unique de la nouvelle association antiparasitaire. L'évaluation du succès clinique chez les chats traités par NexGard® Combo était de 14,3 %, 42,8 %, 100 % et 100 %, respectivement 14, 27/28, 42 et 56 jours après le traitement. Aucun problème de santé n'a été observé tout au long de l'étude.

Gamithromycin in sheep: Pharmacokinetics and clinical evaluation against ovine footrot.

In the context of a development program to obtain the market authorization of injectable gamithromycin 15% w/v solution (Zactran®, Boehringer Ingelheim) for use in sheep against footrot, the pharmacokinetic profile of gamithromycin was established and the safety and efficacy of the treatment were confirmed in a multicenter field study in Europe. The basic pharmacokinetic parameters established in healthy young Merino sheep administered gamithromycin at 6 mg/kg body weight based on the analysis of plasma samples which were collected in intervals up to 12 days after subcutaneous injection were: area under the curve until last quantifiable concentration, 8.88 ± 2.33 µg*h/mL; maximum plasma concentration, 448 ± 180 ng/mL; terminal half-life, 42.5 ± 5.25 h. The safety and clinical efficacy against footrot of gamithromycin 15% w/v solution were evaluated in comparison to tilmicosin 30% w/v solution (Micotil®, Elanco) treatment in 364 sheep of various breeds, sex and age from commercial farms in the United Kingdom (2 sites), Germany (3 sites) and France (1 site). Animals were enrolled based on lesions characteristic of footrot and lameness associated with the presence of footrot-related bacterial pathogens and were randomly allocated and treated in a 1:1 ratio with a single subcutaneous dose of gamithromycin or tilmicosin at label dosage (6 or 10 mg/kg body weight, respectively). Lameness and footrot lesions were evaluated at five and 21 days after treatment; the injection site in all animals was examined the day after treatment and followed up daily in the animals with injection site reaction until complete injection site reaction resolution. Samples of 310 and 120 animals tested positive for Dichelobacter nodosus and Fusobacterium necrophorum, respectively, at inclusion, and data of 359 animals were included into the combined analyses (5 animals excluded for unintentional overdosing [1], lack of follow-up [1], concurrent antibiotic medication for non-footrot conditions [3]). Lameness scores at 21 days after treatment demonstrated a significantly (p = 0.0396) better success for the gamithromycin treatment compared to the tilmicosin treatment (97.8% vs. 93.3%). Post-dosing footrot lesion scores followed similar trends of rapid and marked decrease (improvement) for both treatments with similar (p = 0.127) treatment success for the gamithromycin and tilmicosin treatments (97.8% and 96.0%, respectively). Both treatments were safe; injection site reactions noted in 19 gamithromycin- and 25 tilmicosin-treated animals resolved within five days or six days of treatment, respectively. Gamithromycin 15% w/v solution administered once to sheep by subcutaneous injection at 6 mg/kg body weight demonstrated a pharmacokinetic profile similar to that reported previously in sheep and cattle and was confirmed to be a safe and efficacious treatment for naturally occurring ovine footrot in a multicenter clinical field study conducted in Europe.

Efficacy against nematode and cestode infections and safety of a novel topical fipronil, (S)-methoprene, eprinomectin and praziquantel combination product in domestic cats under field conditions in Europe.

A novel topical combination product (BROADLINE(®), Merial) composed of fipronil, (S)-methoprene, eprinomectin and praziquantel was evaluated for safety and efficacy against nematode and cestode infections in domestic cats. The study comprised a multi-centre, positive control, blinded, field study, using a randomized block design based on order of presentation for allocation. In total 196 client-owned cats, confirmed as positive for naturally acquired infections of nematodes and/or cestodes by pre-treatment faecal examination, were studied in seven countries in Europe. Pre-treatment faecal examination revealed the presence of Toxocara, hookworm, Capillaria and/or spirurid nematode infections in 129, 73, 33 or 1 cat(s), respectively; infections with taeniid and Dipylidium cestodes were demonstrated in 39 and 17 cats, respectively. Cats were allocated randomly to one of two treatments in a ratio of 2, topical fipronil (8.3%, w/v), (S)-methoprene (10%, w/v), eprinomectin (0.4%, w/v) and praziquantel (8.3%, w/v) (BROADLINE(®), Merial; 130 cats); and 1, topical PROFENDER(®) Spot-On (Bayer; 66 cats) and treated once on Day 0. For evaluation of efficacy, two faecal samples were collected, one prior to treatment (Day -4 ± 4 days) and one at the end of the study (Day 14 ± 5 days). These were examined for fecal forms of nematode and cestode parasites. For evaluation of safety, cats were examined by a veterinarian before treatment and at the end of the study, and cat owners recorded the health status of their cats daily until the end of the study. For cats treated with Broadline(®), the efficacy was >99.9%, 100%, and 99.6% for Toxocara, hookworms, and Capillaria, respectively; and the efficacy was >99.9%, >99.9%, and 98.5%, respectively, for the cats treated with Profender(®) (p<0.001 for all nematodes and both treatments). Efficacy was 100% for both cestodes for both treatments (p<0.001). No treatment related adverse experiences were observed throughout the study. For both treatments, every cat that completed the study was given a safety score of 'excellent' for both local and systemic evaluations. The topical combination product of fipronil, (S)-methoprene, eprinomectin and praziquantel was shown to have an excellent safety profile and demonstrated high levels of efficacy when administered once as topical solution to cats infected with nematodes and cestodes under field conditions.