Temmerman Robin, Pelligand Ludovic, Schelstraete Wim, Antonissen Gunther, Garmyn An, Devreese Mathias
Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium.
Department of Clinical Sciences and Services, Royal Veterinary College, University of London, Hawkshead Lane, Hatfield AL9 7TA, UK.
Antibiotics (Basel). 2021 May 19;10(5):604. doi: 10.3390/antibiotics10050604.
Enrofloxacin is frequently administered via drinking water for the treatment of colibacillosis in broiler chickens. However, the EMA/CVMP has urged to re-evaluate historically approved doses, especially for antimicrobials administered via drinking water. In response, the objectives of this study were two-fold. First, to evaluate the pharmacokinetics (PK) of enrofloxacin following IV, PO and drinking water administration. Second, to predict the efficacy of a range of doses in the drinking water for the treatment of APEC infections. For the first objective, PK parameters were estimated by fitting a one-compartmental model with a zero-order IV infusion and an oral absorption lag function to the simultaneously modelled IV and PO data. After fixing these parameter values, a drinking behaviour pharmacokinetic (DBPK) model was developed for the description and prediction of drinking water PK profiles by adding three model improvements (different diurnal and nocturnal drinking rates, inter-animal variability in water consumption and taking account of dose non-proportionality). The subsequent simulations and probability of target attainment (PTA) analysis predicted that a dose of 12.5 mg/kg/24 h is efficacious in treating colibacillosis with an MIC up to 0.125 μg/mL (ECOFF), whereas the currently registered dose (10 mg/kg/24 h) reaches a PTA of 66% at ECOFF.
恩诺沙星常用于通过饮水给药来治疗肉鸡的大肠杆菌病。然而，欧洲药品管理局/兽药委员会已敦促重新评估历史批准剂量，特别是对于通过饮水给药的抗菌药物。对此，本研究有两个目标。第一，评估静脉注射、口服和饮水给药后恩诺沙星的药代动力学（PK）。第二，预测一系列饮水剂量对治疗禽致病性大肠杆菌（APEC）感染的疗效。对于第一个目标，通过将具有零级静脉输注和口服吸收滞后函数的单室模型拟合到同时建模的静脉注射和口服数据来估计PK参数。固定这些参数值后，通过添加三个模型改进（不同的昼夜饮水速率、动物间饮水量的变异性以及考虑剂量非比例性），开发了一个饮水行为药代动力学（DBPK）模型，用于描述和预测饮水PK曲线。随后的模拟和达标概率（PTA）分析预测，剂量为12.5mg/kg/24h对治疗最低抑菌浓度高达0.125μg/mL（生态学临界浓度）的大肠杆菌病有效，而目前注册的剂量（10mg/kg/24h）在生态学临界浓度下的达标概率为66%。
