Zhao Dong-Hao, Wang Xu-Feng, Wang Qiang, Li Liu-Dong
Key Laboratory of Aquatic Product Processing, Ministry of Agriculture, Guangzhou, People's Republic of China.
Laboratory of Quality & Safety Risky Assessment for Aquatic Product on Storage and Preservation, Guangzhou, People's Republic of China.
BMC Vet Res. 2017 Jul 28;13(1):226. doi: 10.1186/s12917-017-1148-7.
The objective of this study is to investigate pharmacokinetics and dose regimens of cefquinome in black swans following intravenous (IV) and intramuscular (IM) administration at a single dose of 2 mg/kg. The MICs of cefquinome against 49 Escherichia coli isolates from black swans were determined. Monte Carlo simulation was applied to conduct the dose regimen assessment and optimization of cefquinome against E. coli in black swans, and a pharmacokinetic/pharmacodynamic (PK/PD) cutoff was established for E. coli isolates obtained in this study.
The PK parameters of T (0.31 h), T (1.69 h) and Cl (0.13 L/kg·h) indicated a rapid distribution and elimination of cefquinome in black swans after IV administration. After IM injection, the corresponding PK parameters of T, T, T, C, and F were 0.12 h, 1.62 h, 0.39 h, 5.71 μg/mL and 74.2%, respectively. The MICs of cefquinome against black swans E. coli ranged from 0.03 to 8 μg/mL, with MIC and MIC of 0.06 and 0.5 μg/mL, respectively. The PK/PD cutoff of cefquinome against E. coli was determined to be 0.2 μg/mL. Monte Carlo simulation showed that the nominal dose regimen (2 mg/kg/24 h) could not achieve a satisfactory probability of target attainment (PTA) for %T ≥ 50%, indicating a risk of treatment failure and the development of potential drug resistance.
The current daily dosage of cefquinome when divided into 12-h interval (1 mg/kg/12 h) may be effective for the treatment of E. coli infections with an MIC ≤0.5 μg/mL.
本研究的目的是调查在以2毫克/千克单剂量静脉注射(IV)和肌肉注射(IM)后,头孢喹肟在黑天鹅体内的药代动力学和给药方案。测定了头孢喹肟对49株从黑天鹅分离出的大肠杆菌的最低抑菌浓度(MIC)。应用蒙特卡洛模拟对头孢喹肟针对黑天鹅大肠杆菌的给药方案进行评估和优化,并为本研究中获得的大肠杆菌分离株建立药代动力学/药效学(PK/PD)界值。
静脉注射后,T(0.31小时)、T(1.69小时)和Cl(0.13升/千克·小时)的药代动力学参数表明头孢喹肟在黑天鹅体内分布和消除迅速。肌肉注射后,T、T、T、C和F的相应药代动力学参数分别为0.12小时、1.62小时、0.39小时、5.71微克/毫升和74.2%。头孢喹肟对黑天鹅大肠杆菌的MIC范围为0.03至8微克/毫升,MIC和MIC分别为0.06和0.5微克/毫升。头孢喹肟针对大肠杆菌的PK/PD界值确定为0.2微克/毫升。蒙特卡洛模拟表明,标称给药方案(2毫克/千克/24小时)对于%T≥50%无法达到令人满意的达标概率(PTA),表明存在治疗失败和潜在耐药性发展的风险。
目前将头孢喹肟每日剂量分为12小时间隔(1毫克/千克/12小时)可能对治疗MIC≤0.5微克/毫升的大肠杆菌感染有效。