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山羊单次及重复静脉注射马波沙星后的药代动力学-药效学整合

Pharmacokinetic-pharmacodynamic integration of marbofloxacin after single and repeated intravenous administration in goats.

作者信息

Bhardwaj Pallavi, Sidhu Pritam K, Lonare M K, Kaur Rajdeep, Dumka V K, Rampal S

机构信息

Department of Veterinary Pharmacology and Toxicology, Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana, Punjab, India; Dept. of Veterinary Pharmacology and Toxicology, Dr. G.C. Negi College of Veterinary and Animal Sciences, CSK H.P. Agricultural University, Palampur, H.P., India.

Institute of Computational Comparative Medicine, College of Veterinary Medicine, P222A, Mosier Hall, Kansas State University, Manhattan KS-66506. USA.

出版信息

Res Vet Sci. 2018 Dec;121:111-115. doi: 10.1016/j.rvsc.2018.10.010. Epub 2018 Oct 22.

Abstract

The single dose pharmacokinetics (PK) of marbofloxacin was compared with repeated intravenous (IV) administrations in six healthy goats at the dose rate of 2 mg/kg body weight at 24 h interval for 5 days. Blood samples were collected at times: 5, 15, 30 min and 1, 2, 4, 6, 9, 12, 24, 36, 48 and 72 h post drug administration. Plasma drug concentrations were determined by High Performance Liquid Chromatography and concentration-time data were subjected to non-compartment analysis. The MIC and MBC of marbofloxacin against Escherichia (E.) coli and Pasteurella (P.) multocida in Mueller Hinton Broth were determined by broth microdilution method. The t = 4.37 ± 0.18 h and Cl = 0.29 ± 0.01 following single administration were not significantly different from t = 5.11 ± 0.22 h and Cl = 0.26 ± 0.01 mL/kg/h after repeated administrations of marbofloxacin. Accumulation index (AI = 1.1) indicated no accumulation of marbofloxacin following repeated IV administrations up to 5 days. The respective MICs of marbofloxacin against E. coli and P. multocida were 0.03 μg/mL and 0.4 μg/mL. The AUC/MIC ratios were 226.64 ± 7.21 h for E. coli and 16.99 ± 0.541 h for P. multocida. PK/PD integration indicated that marbofloxacin daily dose of 2 mg/kg is appropriate for treating E. coli (MIC ≤ 0.03 μg/mL) infections. However, a higher dose of 6 mg/kg/day is suggested to obtain clinical cure against diseases caused by P. multocida having MIC = 0.12 μg/mL in goat species.

摘要

在6只健康山羊中,以2毫克/千克体重的剂量率,每隔24小时重复静脉给药5天,比较了单剂量和重复给药的麻保沙星药代动力学(PK)。在给药后5、15、30分钟以及1、2、4、6、9、12、24、36、48和72小时采集血样。通过高效液相色谱法测定血浆药物浓度,并对浓度-时间数据进行非房室分析。采用肉汤微量稀释法测定麻保沙星对大肠埃希菌和多杀性巴氏杆菌在Mueller Hinton肉汤中的最低抑菌浓度(MIC)和最低杀菌浓度(MBC)。单剂量给药后的t = 4.37±0.18小时和清除率(Cl)= 0.29±0.01与重复给药后麻保沙星的t = 5.11±0.22小时和Cl = 0.26±0.01毫升/千克/小时无显著差异。蓄积指数(AI = 1.1)表明,重复静脉给药达5天,麻保沙星无蓄积。麻保沙星对大肠埃希菌和多杀性巴氏杆菌的各自MIC分别为0.03微克/毫升和0.4微克/毫升。大肠埃希菌的AUC/MIC比值为226.64±7.21小时,多杀性巴氏杆菌为16.99±0.541小时。PK/PD整合表明,麻保沙星每日2毫克/千克的剂量适用于治疗大肠埃希菌(MIC≤0.03微克/毫升)感染。然而,建议使用更高剂量6毫克/千克/天,以获得对山羊体内MIC = 0.12微克/毫升的多杀性巴氏杆菌引起的疾病的临床治愈。

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