Pharmacokinetics/pharmacodynamics of marbofloxacin in a Pasteurella multocida serious murine lung infection model.
Pharmacokinetics/pharmacodynamics of marbofloxacin in a Pasteurella multocida serious murine lung infection model.
复制标题
马波沙星在多杀性巴氏杆菌严重小鼠肺部感染模型中的药代动力学/药效学
DOI：
10.1186/s12917-015-0608-1
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发表时间：
2015-12-02
影响因子：
2.6
通讯作者：
Zeng Z
中科院分区：
文献类型：
--
作者：
Qu Y;Qiu Z;Cao C;Lu Y;Sun M;Liang C;Zeng Z
马波沙星是一种专为兽医学研发的第三代氟喹诺酮类药物，对一些革兰氏阳性菌和大多数革兰氏阴性菌具有广谱抗菌活性，包括牛呼吸道病原体多杀性巴氏杆菌。我们研究的目的是阐明马波沙星在多杀性巴氏杆菌感染的小鼠肺部模型中的药代动力学和药效学，并评估与各种效应相关的药代动力学 - 药效学参数的大小。
药代动力学研究表明，在感染小鼠中，马波沙星在1.25至10毫克/千克体重的剂量范围内呈线性动力学。中性粒细胞减少感染小鼠血浆中的蛋白质结合率为29.77%。与抑菌效应、细菌计数减少2个对数10和减少3个对数10相关的24小时内游离药物浓度 - 时间曲线下面积与最低抑菌浓度的比值（fAUC0 - 24h/MIC）分别为40.84、139.34和278.08小时。
基于剂量范围研究，马波沙星呈现浓度依赖性杀菌作用，fAUC/MIC是与疗效相关性最佳的药代动力学/药效学指标（R² = 83%）。基于fAUC0 - 24h/MIC为278.08小时的杀菌效应目标，如果马波沙星用于治疗MIC90为0.12微克/毫升的多杀性巴氏杆菌严重肺部感染，目前的剂量（2毫克/千克）将无法达到杀菌效果。使用比临床实践中常用剂量更高的剂量（4 - 6毫克/千克）会更有益。
本文的在线版本（doi:10.1186/s12917 - 015 - 0608 - 1）包含补充材料，授权用户可获取。
BackgroundMarbofloxacin is a third-generation fluoroquinolone developed solely for veterinary medicine with a broad spectrum of antibacterial activity against some Gram-positive and most Gram-negative bacteria, including the bovine respiratory tract pathogen, Pasteurella multocida. The objective of our study was to elucidate the pharmacokinetics and pharmacodynamics of marbofloxacin in a Pasteurella multocida infected murine lung model, and to estimate the magnitudes of pharmacokinetics-pharmacodynamics parameters associated with various effects.ResultsThe pharmacokinetic studies revealed marbofloxacin kinetics in infected mice were linear over a dose ranging from 1.25 to 10 mg/kg of body weight. The protein binding in the plasma of neutropenic infected mice was 29.77 %. The magnitudes of the ratio of the free-drug area under the concentration-time curve over 24 h to MIC (fAUC0-24h/MIC) associated with static effect, a 2 log10 reduction and a 3 log10 reduction of bacterial counts were 40.84, 139.34, and 278.08 h, respectively.Conclusions On the basis of a bactericidal effect goal of fAUC0-24h/MIC of 278.08 h, if marbofloxacin is used for the treatment of P. multocida serious lung infection with an MIC90 of 0.12 μg/ml, the current dose (2 mg/kg) would fail to achieve a bactericidal effect. It would benefit from higher doses (4 ~ 6 mg/kg) than those commonly used in clinical practice.