Boehringer Ingelheim Vetmedica GmbH, Rohrdorf, Germany.
Boehringer Ingelheim Animal Health France, Lyon, France.
Vet Med Sci. 2021 Mar;7(2):455-464. doi: 10.1002/vms3.375. Epub 2020 Oct 15.
The pharmacokinetics of gamithromycin were evaluated in 26 male castrated and female crossbred swine administered gamithromycin 15% w/v (Zactran®, Boehringer Ingelheim) intravenously at 6 mg/kg bodyweight or intramuscularly at 3, 6 or 12 mg/kg bodyweight. Blood samples were collected up to Day 10 to establish the plasma profile of gamithromycin, bioavailability and dose proportionality. When administered by intramuscular injection at 6 mg/kg BWT, pharmacokinetic parameters were as follows: area under the curve until last quantifiable plasma concentration, 5.13 ± 0.957 µg*hours/ml; maximum plasma concentration, 960 ± 153 ng/ml at 5 to 15 min; terminal half-life of 94.1 ± 20.4 hr. Absolute bioavailability was 92.2%. Increase in systemic exposure was proportional to the gamithromycin dose level over the range 3-12 mg/kg BWT. No gender-related statistically significant difference in exposure was observed. For clinical evaluation of Zactran® against swine respiratory disease, 305 pigs from six commercial farms in three countries in Europe with signs associated with Actinobacillus pleuropneumoniae and/or Haemophilus parasuis and/or Pasteurella multocida and/or Bordetella bronchiseptica were used. At each site, animals were treated once in a 1:1 ratio with a single intramuscular dose of Zactran® (6 mg gamithromycin/kg bodyweight) or Zuprevo® (4% w/v tildipirosin at 4 mg/kg bodyweight; MSD Animal Health) at the recommended dose respectively. Animals were observed and scored daily for 10 consecutive days for signs of swine respiratory disease (depression, respiration and rectal temperature), and animals presenting signs of clinical swine respiratory disease (Depression Score 3 and/or Respiratory Score 3 associated with Rectal Temperature > 40.0°C) were removed from the study and considered as treatment failure. Animals which remained in the study were individually assessed for 'treatment success' or 'treatment failure' (Depression Score ≥ 1 and Rectal Temperature > 40.0°C or Respiratory Score ≥ 1 and Rectal Temperature > 40.0°C). Using a non-inferiority hypothesis test (non-inferiority margin = 0.10), the proportion of treatment successes in the Zactran® group (97%) was equivalent to or better than that in the Zuprevo® group (93%).
加米霉素的药代动力学在 26 头去势雄性和雌性杂交猪中进行评估，这些猪分别静脉内给予 6mg/kg 体重的 15% w/v 加米霉素（Zactran ® ，勃林格殷格翰）或肌肉内给予 3、6 或 12mg/kg 体重的加米霉素。采集血液样本至第 10 天，以建立加米霉素的血浆药代动力学特征、生物利用度和剂量比例关系。当以 6mg/kg 体重的肌内注射给予时，药代动力学参数如下：直至最后可定量的血浆浓度的曲线下面积，5.13±0.957μg*小时/ml；最大血浆浓度，在 5 至 15 分钟时为 960±153ng/ml；半衰期为 94.1±20.4 小时。绝对生物利用度为 92.2%。在 3 至 12mg/kg 体重范围内，系统暴露量的增加与加米霉素剂量水平成正比。未观察到与性别相关的暴露量有统计学意义的差异。为了评估 Zactran ® 对猪呼吸道疾病的临床疗效，在欧洲三个国家的六个商业化农场中，使用了 305 头有胸膜肺炎放线杆菌和/或副猪嗜血杆菌和/或多杀巴斯德菌和/或支气管败血波氏杆菌相关临床症状的猪。在每个地点，动物按 1:1 的比例用单剂量的肌内注射 Zactran ® （6mg 加米霉素/kg 体重）或 Zuprevo ® （4% w/v 替米考星，4mg/kg 体重；默沙东动物保健）进行治疗，剂量分别为推荐剂量。动物每天观察和评分 10 天，以评估猪呼吸道疾病的临床症状（抑郁、呼吸和直肠温度），出现猪呼吸道疾病临床症状（抑郁评分 3 分和/或呼吸评分 3 分，伴有直肠温度>40.0°C）的动物将从研究中剔除，并视为治疗失败。留在研究中的动物将单独评估“治疗成功”或“治疗失败”（抑郁评分≥1 分，直肠温度>40.0°C 或呼吸评分≥1 分，直肠温度>40.0°C）。使用非劣效性假设检验（非劣效性边界=0.10），Zactran ® 组（97%）的治疗成功率与 Zuprevo ® 组（93%）相当或更高。
