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...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 the drug.展开更多
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<sup...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<sup>®</sup> (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<sup>®</sup> (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<sup>®</sup> and ≥93.7% for NexGard Spectra<sup>®</sup>. Consistent results were observed along all the observation periods with final efficacies (day 30) of ≥99.8% and 98.3% for NexGard<sup>®</sup> and NexGard Spectra<sup>®</sup>, respectively. In conclusion, both NexGard<sup>®</sup> and Nexgard Spectra<sup>®</sup> provided a curative effect and sustained efficacy against Rhipicephalus sanguineus for at least 30 days in highly contaminated shelter environments.展开更多
基金Supported by Natural Science Fund of Heilongjiang Province(C201424)
文摘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 the drug.
文摘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<sup>®</sup> (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<sup>®</sup> (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<sup>®</sup> and ≥93.7% for NexGard Spectra<sup>®</sup>. Consistent results were observed along all the observation periods with final efficacies (day 30) of ≥99.8% and 98.3% for NexGard<sup>®</sup> and NexGard Spectra<sup>®</sup>, respectively. In conclusion, both NexGard<sup>®</sup> and Nexgard Spectra<sup>®</sup> provided a curative effect and sustained efficacy against Rhipicephalus sanguineus for at least 30 days in highly contaminated shelter environments.
