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Efficacy of Afoxolaner Alone or in Combination with milbemycin oxime against Rhipicephalus sanguineus Lato Sensu in Naturally Infested Dogs in Colombia

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Open Journal of Veterinary Medicine 2022年第4期12卷 27-36页

作者： Victor Molina Diego Pérez Jorge Prada Luis Carlos Perez Cogollo Natalia Pedraza Francisco Perozo Frederic Beugnet Boehringer Ingelheim Animal Health Bogotà Colombia University of Medellín Medellín Antioquia Colombia University of Córdoba Montería Colombia University of the Llanos Villavicencio Meta Colombia

The brown dog tick (Rhipicephalus sanguineus lato sensu) is the tick that most affects dogs worldwide and is therefore the main blood pathogen vector in dogs. The efficacy of afoxolaner 2.7 to 7.1 mg/kg NexGard® (group A) and afoxolaner plus milbemycin oxime 2.5 to 5.4 mg/kg and 0.5 to 1.1 mg/kg respectively NexGard Spectra® (Group B) against R. sanguineus, was evaluated in naturally infected sheltered dogs under high challenging conditions in four different areas of Colombia (Antioquia, Córdoba, Santander, and Meta). Tick counts (alive, dead, attached, and unattached) were performed on treated dogs, the average was calculated for the different areas to evaluate the efficacy of each treatment at six different times post-treatment (24 h, 48 h, 7 d, 14 d, 21 d, 30 d). None of the dogs showed adverse events related to the treatments. The average tick number pre-treatment was 68 in group A and 78.3 for group B indicating a strong natural infection of the dogs and their environment. Efficacy after 24 h against R. sanguineus was always above 90% with ≥97.4% for NexGard® and ≥93.7% for NexGard Spectra®. Consistent results were observed along all the observation periods with final efficacies (day 30) of ≥99.8% and 98.3% for NexGard® and NexGard Spectra®, respectively. In conclusion, both NexGard® and Nexgard Spectra® provided a curative effect and sustained efficacy against Rhipicephalus sanguineus for at least 30 days in highly contaminated shelter environments.

关键词： Afoxolaner milbemycin oxime Rhipicephalus sanguineus Dogs Shelter

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Pharmacokinetics of milbemycin oxime in Dogs Following Its Intravenous and Oral Administration

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Journal of Northeast Agricultural University(English Edition) 2018年第1期25卷 47-54页

作者： Lu Yi-tong Qi Lian-wen Xu Qian-qian Ding Liang-jun Wang Bo Liu Hai-rui Li Ji-chang State Key Laboratory of Natural Medicines China Pharmaceutical UniversityNanjing 211198China College of Veterinary Medicine Northeast Agricultural UniversityHarbin 150030China Shandong Binzhou Animal Science and Veterinary Medicine Academy Binzhou 256600ShandongChina

The pharmacokinetics of milbemycin oxime was investigated in dogs following oral(per os, PO) and intravenous(IV) administration. Three groups of dogs received milbemycin oxime tablets as a single PO dose equal to 0.25, 0.5 and 1.0 mg · kg-1 of milbemycin oxime, respectively, another group received a single IV dose of 0.5 mg · kg-1. Blood samples were collected at predetermined times after drug administration and the milbemycin oxime concentrations in plasma were determined by LC-MS/MS. The drug protein binding in dog plasma in vitro was determined by equilibrium dialysis at concentrations spanning the range of values observed in vivo in dog plasma. After PO administration at doses of 0.25, 0.5 and 1.0 mg · kg-1, milbemycin oxime was slowly absorbed and eliminated, the time to reach the maximum plasma concentration(Tmax) was 4.14±0.20, 4.27±0.14 and 4.06±0.13 h, the mean absorption time(MAT) was 19.06, 13.67 and 11.77 h, the terminal rate half-life(t1/2λz) was 15.06±0.37, 11.09±0.54 and 9.76±0.89 h and the total body clearance(Cl) was 1.15±0.05, 1.18±0.03 and 1.17±0.07 m L · min-1 · kg-1, respectively. The maximum plasma concentration(Cmax, 36.50±1.40, 76.11±2.77 and 182.05±7.20 ng · m L-1, respectively) and the area under the first-moment curve(AUC-10→∞, 985.83±49.46, 1 663.12±51.42 and 3 558.04±197.88 mg · h · L, respectively) increased accordingly to the administered dose rates; the oral bioavailabilities were estimated to be 88.61%, 74.75% and 79.96%, respectively. The values of fu were 0.12%, 0.14% and 0.13% in dog plasma, respectively. In conclusion, the pharmacokinetics of milbemycin oxime in dogs following oral administration revealed its higher oral bioavailability and advantageous pharmacokinetic properties, such as its lower total body clearance and longer elimination half-life, and indicated that the single oral dose of 0.50 mg · kg-1 of milbemycin oxime which was recommended in all the parasitological efficacy studies allowed an adequate concentration of

关键词： pharmacokinetic macrolide milbemycin oxime oral administration dog

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Effect of milbemycin oxime on Toxocara canis Eggs and Larvae

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Journal of Northeast Agricultural University(English Edition) 2020年第2期27卷 130-135页

作者： Hu Wan-jun Ding Liang-jun Chen Chun-li Xu Jia Li Ji-chang College of Veterinary Medicine Northeast Agricultural UniversityHarbin 150030China College of Life Sciences Northeast Agricultural UniversityHarbin 150030China Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development Harbin 150030China Raohe Customs District P.R.China Shuangyashan 155700HeilongjiangChina

Toxocara canis(***)is one of the most important zoonotic parasites of *** aim of the present study was to perform an in vitro analysis of the effect of milbemycin oxime on *** eggs following exposure to a concentration gradient of the drug and to determine the inflammatory reaction produced by the infective *** larvae in *** present study was undertaken using the model nematode,***,to investigate the effect of milbemycin oxime on *** eggs and *** eggs were exposed to a concentration gradient of milbemycin oxime in vitro,the higher concentration of milbemycin oxime was,the lower percentage of infective stage larvae *** micrographs showed that milbemycin oxime induced eggs dissolved and eggshell *** analyses of mice that stained with hematoxylin and eosin(H&E)showed in lower dosing(10-7 and 10-8 g·mL-1)drug-treated groups,atrophy of alveolar space and interalveolar septum thickening appeared,inflammatory infiltrates accompanied with erythrocytes around blood vessels and bronchioles *** higher dosing(10-6,10-5 and 10-4 g·mL-1)drug-treated groups,low-grade or no pathological changes occurred,indicating that milbemycin oxime could obviously decrease the inflammatory reaction produced by the infection of *** larvae in vivo.

关键词： in vitro in vivo milbemycin oxime Toxocara canis

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