bay-44-4400 and moxidectin

A spot-on formulation containing fluralaner (280 mg/ml) plus moxidectin (14 mg/ml) (Bravecto® Plus) was developed for the treatment of nematode infections as well as providing 12 weeks of protection against insect and acarine parasites in cats. The effectiveness and safety of this product against feline gastrointestinal nematodes was assessed in naturally-infested, client-owned cats under field conditions in Albania, Bulgaria, Germany and Hungary.. To be eligible for enrollment in this investigator-blinded study cats had to be at least 10 weeks-old, weigh at least 1.2 kg, be clinically healthy, and have a faecal sample testing positive for nematodes no more than eight days prior to treatment. Cats were stratified into blocks of three in order of presentation at each center and randomly allocated in a 2:1 ratio to be treated topically on Day 0 with fluralaner plus moxidectin (minimum dose rates 40 mg/kg and 2 mg/kg, respectively) or emodepside plus praziquantel (minimum dose rates 3 mg/kg and 12 mg/kg, respectively) (Profender®). Faecal samples were collected from cats prior to treatment and 14 ± 4 days later.. There were 182 cats randomized to the fluralaner plus moxidectin group, and 91 to the emodepside plus praziquantel group. Prior to treatment the most commonly identified nematode egg was Toxocara cati, found in 79.1 and 82.4% of cats in the fluralaner plus moxidectin and emodepside plus praziquantel groups, respectively. Eggs of Toxascaris leonina were found in 8.2 and 6.6% of cats; of hookworms in 30.8 and 24.2%; and of Capillaria spp. in 7.1 and 4.3%, respectively. After treatment, faecal samples from 98.3% of fluralaner plus moxidectin treated and 96.6% of emodepside plus praziquantel-treated cats were free of nematode ova. Geometric mean faecal egg count reductions for T. cati, the only eggs found in post-treatment faecal samples, were 99.97% and 99.93%, respectively. Treatment with fluralaner plus moxidectin was non-inferior to emodepside plus praziquantel. Both products were safe and well tolerated by cats treated under field conditions.. This field study confirms that, in addition to 12-week extended duration flea and tick control, fluralaner plus moxidectin provides broad spectrum treatment of nematodes in cats.

Topics: Administration, Topical; Animals; Cat Diseases; Cats; Depsipeptides; Europe, Eastern; Feces; Female; Germany; Insecticides; Isoxazoles; Macrolides; Nematoda; Nematode Infections; Parasite Egg Count; Praziquantel; Random Allocation; Single-Blind Method; Siphonaptera; Treatment Outcome

Several issues have been identified with the current programs for the elimination of onchocerciasis that target only transmission by using mass drug administration (MDA) of the drug ivermectin. Alternative and/or complementary treatment regimens as part of a more comprehensive strategy to eliminate onchocerciasis are needed. We posit that the addition of "prophylactic" drugs or therapeutic drugs that can be utilized in a prophylactic strategy to the toolbox of present microfilaricidal drugs and/or future macrofilaricidal treatment regimens will not only improve the chances of meeting the elimination goals but may hasten the time to elimination and also will support achieving a sustained elimination of onchocerciasis. These "prophylactic" drugs will target the infective third- (L3) and fourth-stage (L4) larvae of Onchocerca volvulus and consequently prevent the establishment of new infections not only in uninfected individuals but also in already infected individuals and thus reduce the overall adult worm burden and transmission. Importantly, an effective prophylactic treatment regimen can utilize drugs that are already part of the onchocerciasis elimination program (ivermectin), those being considered for MDA (moxidectin), and/or the potential macrofilaricidal drugs (oxfendazole and emodepside) currently under clinical development. Prophylaxis of onchocerciasis is not a new concept. We present new data showing that these drugs can inhibit L3 molting and/or inhibit motility of L4 at IC50 and IC90 that are covered by the concentration of these drugs in plasma based on the corresponding pharmacological profiles obtained in human clinical trials when these drugs were tested using various doses for the therapeutic treatments of various helminth infections.

Topics: Animals; Benzimidazoles; Depsipeptides; Filaricides; Humans; Ivermectin; Larva; Leukocytes, Mononuclear; Macrolides; Onchocerca volvulus; Onchocerciasis

The aim of this study was to sequence all exons of the ABCB1 (MDR1) gene in cats that had experienced adverse reactions to P-glycoprotein substrate drugs (phenotyped cats). Eight phenotyped cats were included in the study consisting of eight cats that experienced central nervous system toxicosis after receiving ivermectin (n = 2), a combination product containing moxidectin and imidacloprid (n = 3), a combination product containing praziquantel and emodepside (n = 1) or selamectin (n = 2), and 1 cat that received the product containing praziquantel and emodepside but did not experience toxicity (n = 1). Fifteen exons contained polymorphisms and twelve exons showed no variation from the reference sequence. The most significant finding was a nonsense mutation (ABCB11930_1931del TC) in one of the ivermectin-treated cats. This cat was homozygous for the deletion mutation. All of the other phenotyped cats were homozygous for the wild-type allele. However, 14 missense mutations were identified in one or more phenotyped cats. ABCB11930_1931del TC was also identified in four nonphenotyped cats (one homozygous and three heterozygous for the mutant allele). Cats affected by ABCB11930_1931del TC would be expected to have a similar phenotype as dogs with the previously characterized ABCB1-1Δ mutation.

Topics: Animals; ATP Binding Cassette Transporter, Subfamily B; Cat Diseases; Cats; Central Nervous System Diseases; Cloning, Molecular; Codon, Nonsense; Depsipeptides; Exons; Homozygote; Imidazoles; Ivermectin; Macrolides; Neonicotinoids; Nitro Compounds; Polymorphism, Single Nucleotide; Praziquantel; Sequence Analysis, DNA

Safety of concomitant use of veterinary products is of clinical interest. A series of studies was performed to evaluate the chemical compatibility and short term dermal and systemic safety of an imidacloprid/flumethrin collar (Seresto(®)/ Foresto(®), Bayer) used concomitantly with spot-on or tablet formulations.Chemical compatibility was evaluated in-vitro (study reference A) on collar pieces, followed by two small, non-controlled clinical studies (study reference B) in both, cats and dogs. The studies showed, that certain solvents affected the collar in-vitro, but not in their marketed formulations.Dermal and systemic safety of different spot-on or tablet formulations was first evaluated in a small, non-controlled clinical study (study reference C) in cats and dogs, via clinical observations only, followed by controlled clinical safety studies of concomitant use with imidacloprid/ moxidectin (Advocate(®)/ Advantage(®) Multi, Bayer) in dogs and cats (study reference D) and emodepside/ praziquantel (Profender(®), Bayer) in cats (study reference E), assessing safety aspects by clinical observations and statistical analyses of hematology and clinical chemistry parameters compared to baseline values and between treated and control groups.Dermal safety findings over all clinical studies (study references B to E) matched those already described for the respective products and included transient cosmetic changes (oily hair and crystal formation) at the site of spot-on application and broken hair, transient alopecia and skin alterations at the site of collar application. There were no indications of these findings aggravating under the conditions of concurrent use. There were no systemic safety findings of clinical significance in any of the clinical safety studies (study reference C to E). Assessment of blood parameters revealed some deviations from baseline levels and from the reference range in dogs as well as in cats, but no clinical relevance could be deduced. Hematology and clinical chemistry results confirmed the safety of the concomitant treatment. It is concluded that Seresto(®) is chemically compatible with solvents used in major spot-on formulations on the market and is dermally and systemically safe for adult dogs and cats when used concomitantly with Advocate(®) and Profender(®) spot-on formulations.

Topics: Administration, Topical; Animals; Cat Diseases; Cats; Depsipeptides; Dog Diseases; Dogs; Imidazoles; Insecticides; Macrolides; Neonicotinoids; Nitro Compounds; Praziquantel; Pyrethrins; Solvents