Foster D M, Sylvester H J, Papich M G
Department of Population Health and Pathobiology, College of Veterinary Medicine, NC State University, Raleigh, NC, USA.
Department of Molecular and Biomedical Sciences, College of Veterinary Medicine, NC State University, Raleigh, NC, USA.
J Vet Pharmacol Ther. 2017 Dec;40(6):e45-e53. doi: 10.1111/jvp.12412. Epub 2017 Apr 29.
Antibiotic distribution to interstitial fluid (ISF) and pulmonary epithelial fluid (PELF) was measured and compared to plasma drug concentrations in eight healthy calves. Enrofloxacin (Baytril 100) was administered at a dose of 12.5 mg/kg subcutaneously (SC), and tilmicosin (Micotil 300) was administered at a dose of 20 mg/kg SC. PELF, sampled by two different methods-bronchoalveolar lavage (BAL) and direct sampling (DS)-plasma, and ISF were collected from each calf and measured for tilmicosin, enrofloxacin and its metabolite ciprofloxacin by HPLC. Pharmacokinetic analysis was performed on the concentrations in each fluid, for each drug. The enrofloxacin/ciprofloxacin concentration as measured by AUC in DS samples was 137 ± 72% higher than in plasma, but in BAL samples, this value was 535 ± 403% (p < .05). The concentrations of tilmicosin in DS and BAL samples exceeded plasma drug concentrations by 567 ± 189% and 776 ± 1138%, respectively. The enrofloxacin/ciprofloxacin concentrations collected by DS were significantly different than those collected by BAL, but the tilmicosin concentrations were not significantly different between the two methods. Concentrations of enrofloxacin/ciprofloxacin exceeded the MIC values for bovine respiratory disease pathogens but tilmicosin did not reach MIC levels for these pathogens in any fluids.
在八只健康小牛中测量了抗生素在间质液(ISF)和肺上皮液(PELF)中的分布,并与血浆药物浓度进行了比较。恩诺沙星(拜有利100)以12.5毫克/千克的剂量皮下注射(SC),替米考星(米考星300)以20毫克/千克的剂量皮下注射。通过两种不同方法——支气管肺泡灌洗(BAL)和直接采样(DS)——采集每头小牛的PELF、血浆和ISF,并通过高效液相色谱法测定其中替米考星、恩诺沙星及其代谢产物环丙沙星的含量。对每种药物在每种液体中的浓度进行药代动力学分析。DS样本中通过AUC测得的恩诺沙星/环丙沙星浓度比血浆中高137±72%,但在BAL样本中,该值为535±403%(p<0.05)。DS和BAL样本中替米考星的浓度分别比血浆药物浓度高567±189%和776±1138%。DS采集的恩诺沙星/环丙沙星浓度与BAL采集的浓度有显著差异,但两种方法采集的替米考星浓度无显著差异。恩诺沙星/环丙沙星的浓度超过了牛呼吸道疾病病原体的最低抑菌浓度值,但替米考星在任何液体中都未达到这些病原体的最低抑菌浓度水平。