The objectives of this study were to investigate the pharmacokinetics (PK), pharmacodynamics (PD), and the efficacy of oral administration of doxycycline (DXC) in horses with Streptococcus zooepidemicus tissue infections. Tissue chambers (TC) were implanted subcutaneously in the cervical region of 7 horses and inoculated with a single S. zooepidemicus isolate with a minimum inhibitory concentration (MIC) of 0.25 µg/ml, determined by agar dilution. Doxycycline hyclate (10 mg/kg, orally, q 12 h, for 5 days) mixed with poloxamer gel was started following inoculation. The TC fluid was sampled prior to and following inoculation for cytology analysis, quantitative culture, and DXC determination. Plasma DXC concentrations were measured over 48 h following the last dose of DXC administered. The mean plasma peak concentration (C_max) of DXC was 0.32 µg/ml, and concentrations above the MIC were only reached in 3 TC samples. In plasma, mean T > MIC was 2.4 h, mean C_max/MIC was 1.30, and mean AUC_last/MIC was 11.63 h. These PK/PD indices did not reach the suggested targets for DXC treatments of infections, and the TC abscessed in all horses. This is the first study to evaluate the recommended dose of DXC in horse in an infection model.

中文翻译：

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多西环素在马链球菌亚种中的药代动力学和药效学。马的兽疫病感染模型

本研究的目的是研究口服多西环素 (DXC) 对兽疫链球菌 组织感染马的药代动力学 (PK)、药效学 (PD) 和疗效。将组织室 (TC) 皮下植入 7 匹马的颈部区域并接种单个S。 兽疫通过琼脂稀释确定的最低抑菌浓度 (MIC) 为 0.25 µg/ml。接种后开始使用盐酸多西环素（10 mg/kg，口服，每 12 小时一次，持续 5 天）与泊洛沙姆凝胶混合。在接种之前和之后对 TC 流体进行采样，用于细胞学分析、定量培养和 DXC 测定。在最后一剂 DXC 给药后 48 小时内测量血浆 DXC 浓度。DXC的平均血浆峰浓度 ( C _max ) 为 0.32 µg/ml，只有 3 个 TC 样品达到了高于 MIC 的浓度。在血浆中，平均T  > MIC 为 2.4 小时，平均C _max /MIC 为 1.30，平均 AUC_最后/MIC 是 11.63 小时。这些 PK/PD 指数没有达到 DXC 治疗感染的建议目标，并且所有马的 TC 都出现脓肿。这是第一项在感染模型中评估马中 DXC 推荐剂量的研究。