Clinical field study of the safety and efficacy of spinosad chewable tablets for controlling fleas on dogs.

Preliminary studies showed spinosad to be rapidly effective and safe in controlling fleas on dogs. To validate these studies, a clinical trial was undertaken using 470 flea-infested client-owned dogs allocated to receive three monthly treatments with either beef-flavored chewable spinosad tablets (30-60 mg/kg) or selamectin applied according to label instructions. Flea counts 15 days after enrollment were reduced by 98.6% and 90.9% for spinosad- and selamectin-treated dogs, respectively; at 90 days, flea count reductions were 99.9% and 98.9%, respectively. Compared with baseline, all flea reductions were significant (P < .001) for both products and spinosad was significantly (P ≤ .0172) more effective than selamectin at each postenrollment flea count.

Therapeutic and persistent efficacy of spinosad applied as a pour-on or a topical spray against natural infestations of chewing and sucking lice on cattle.

Studies were conducted in Wisconsin and Illinois, USA, to assess and compare the therapeutic and persistent efficacy of spinosad when applied as either a pour-on or topical spray and compared with cyfluthrin pour-on and coumaphos topical spray for controlling natural infestations of chewing (Bovicola bovis) and sucking (Linognathus vituli, Solenopotes capillatus and Haematopinus eurysternus) lice on cattle. Thirty-five animals at each trial site were blocked according to pre-treatment lice counts and randomly allocated to one of five treatment groups: single treatments of spinosad (25 g/L), diluted with water to 0.04% active ingredient and applied as a whole-body topical spray; spinosad (25 g/L) applied as a neat pour-on at 2 mg/kg body weight; Co-Ral Emulsifiable Livestock Insecticide (5.8% coumaphos), diluted to 0.03% active ingredient and applied as a whole-body topical spray; CyLence Pour-on Insecticide (1% cyfluthrin), applied as a neat pour-on at the manufacturer's recommended use rate for lice; and untreated control. Both spinosad treatments and cyfluthrin provided > or =96% control of B. bovis for up to 7 weeks, whereas the efficacy of coumaphos dropped to <90% after week 5 at one site. Spinosad spray had the best therapeutic and residual control of all treatments against L. vituli, > or =98% for at least 5 weeks at both sites, compared with 3 weeks for coumaphos at one site. Spinosad and coumaphos sprays provided 100% control of S. capillatus for at least 8 weeks compared with > or =97% control for spinosad and cyfluthrin pour-on treatments over the same interval. While H. eurysternus burden was low and limited to one study site, all four treatments provided 100% control for at least 6 weeks. These studies showed that topically applied spinosad provided a high degree of therapeutic and residual control against both sucking and chewing lice.

An in vivo rodent model for identifying and characterizing acaricides.

Evaluation of candidate acaricides in livestock or companion animals is expensive, time-consuming, and usually requires large quantities of test material. To identify promising substances at the earliest possible stage of the development process, robust and predictive surrogate animal models, capable of rapidly characterizing potency with minimal compound requirements, are necessary. The objective of this study was to generate an in vivo surrogate animal bioassay capable of rapidly and accurately predicting the topical activity of acaricides emerging from in vitro acaricide bioassays. The rat acaricide test (RAT) requires adult rats, Rattus norvegicus (Berkenhout, 1769), a flexible tick containment device fastened to their dorso-thoracic region, and the nymphal stage of the lone star tick, Amblyomma americanum (L.). The feeding kinetics of A. americanum nymphs on rats was assessed, and compound efficacies were determined by measuring tick survivorship and engorgement weight on acaricide-treated animals. Results from this bioassay demonstrated efficacy with fipronil, ivermectin, permethrin, and chlorpyrifos, and dose-response relationships for each acaricide were determined. The rank order of potencies was fipronil > ivermectin > chlorpyrifos = permethrin for nymphal mortality and fipronil > ivermectin > chlorpyrifos > permethrin for inhibition of nymphal engorgement. The activity of permethrin against nymphs in the RAT was positively correlated with potency values for technical and commercial permethrin formulations against adult A. americanum infestations on cattle. The RAT proved to be an economical, rapid surrogate animal bioassay that together with the in vitro acaricide bioassay can be used for the rapid identification, characterization, and prioritization of candidate acaricides.

Dose-confirmation studies of the cestocidal activity of pyrantel pamoate paste in horses.

Dose confirmation studies of the cestocidal activity of pyrantel pamoate paste were conducted at two sites in North America during 2001. Horses with naturally-acquired cestode infections were identified by detection of typical Anoplocephala spp. eggs in feces collected between 7 and 92 days prior to treatment. Twenty and 22 horses were enrolled at Site 1 (Urbana, IL) and Site 2 (Knoxville, TN), respectively. Candidate horses were acclimated to study conditions for 14 days, ranked by length of interval since coprologic confirmation, and allocated randomly to one of two treatment groups: (T1) pyrantel pamoate paste 13.2mg pyrantel base per kilogram body weight administered orally, and (T2) untreated controls. Individual doses of pyrantel pamoate paste were prepared on the basis of contemporaneous body weights and administered to Group T1 horses on Day 0. Trained personnel monitored the animals at regular intervals after treatment to detect potential adverse reactions. Horses were euthanatized and necropsied 10-12 days after treatment. The contents of the large and small intestines were collected, and the walls of each organ were rinsed with water and inspected. Attached cestodes were recovered and preserved in 10% formalin. The intestinal contents and rinsed ingesta were washed over a #10-mesh (2mm aperture) sieve and tapeworms were extracted and preserved. Recovered cestodes were counted and examined at 1-4x magnification for identification to genus and species. At Site 1, specimens of Anoplocephala perfoliata were recovered from seven of 10 control horses, and from one of 10 horses treated with pyrantel pamoate. Mean cestode numbers were 4.52 in the control group and 0.07 for treated horses. At Site 2, cestodes were found in 10 of 11 controls (mean 26.2) and in five of 11 horses (mean 1.2) treated with pyrantel pamoate. In both studies, Group T1 means were significantly lower than the control group (P<0.005). The calculated efficacies were 98.4 and 95.5% at Sites 1 and 2, respectively. In two dose-confirmation studies, a single, oral treatment of pyrantel pamoate paste (19.13% w/w pyrantel base) at 13.2mg/kg was >or=95.5% effective against A. perfoliata in naturally-infected horses.

Effects of dermal application of 10.0% imidacloprid-0.08% ivermectin in ivermectin-sensitive Collies.

OBJECTIVE: To evaluate the safety of dermal application of 10.0% imidacloprid-0.08% ivermectin in ivermectin-sensitive Collies at dose rates of 3 to 5 times the proposed maximum therapeutic dose. ANIMALS: 15 Collies (5 males and 10 females) that were confirmed as ivermectin-sensitive dogs. PROCEDURE: Dogs were assigned to 3 treatment groups (control, 3X, or 5X group) in a randomized block design on the basis of the maximal ivermectin-sensitivity score obtained during preliminary screening. Dogs in groups 3X and 5X were treated at 3 and 5 times the maximum label dose, respectively. Control dogs received an application of an equal volume of a nonmedicated solution. Observation and scoring on all days were conducted to specifically include neurologic signs typical of ivermectin toxicosis, including lethargy, ataxia, abnormal mydriasis, and abnormal salivation. RESULTS: None of the dogs had clinical abnormalities during the study period. CONCLUSIONS AND CLINICAL RELEVANCE: Analysis of results of this study indicates that dermal application of 10.0% imidacloprid-0.08% ivermectin is safe for use in ivermectin-sensitive Collies at dose rates of 3 or 5 times the proposed maximum therapeutic dose.