This study was designed to investigate the safety and pharmacokinetic (PK) profile of tildipirosin in horses after intravenous (i.v.) and subcutaneous (s.c.) injection of a single dose at 4 mg/kg of body weight (b.w.). A total of 12 healthy mixed breed horses were used in the study. Horses were monitored for systemic and local adverse effects, and whole blood samples were collected for hematology and plasma biochemistry analysis at time (0) and at 6, 24, and 72 h after drug administration. For PK analysis, blood samples were collected at pre-determined times before and after tildipirosin administration. Plasma concentrations of tildipirosin were determined using ultra-high-performance liquid chromatography–ultraviolet detection method (UHPLC-UV). All horses tolerated the i.v. injection of tildipirosin without showing any systemic adverse effects. However, a non-painful, soft swelling appeared at the s.c. injection site in 5 horses (41.7%). On average, tildipirosin reached a maximum plasma concentration (C_max) of 1257 ng/ml (geometric mean) between 0.5 and 1.5 h after s.c. administration (T_max). The geometric mean values for total body clearance (Cl), the apparent volume of distribution based on the terminal phase (V_z), and the apparent volume of distribution at steady-state (V_ss) were 0.52 L/kg·h, 22 L/kg, and 10.0 L/kg, respectively. Data collected in this study suggests that tildipirosin can be used safely in horses with caution.

中文翻译：

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替地吡罗辛在马中静脉和皮下给药后的药代动力学和生物利用度

本研究旨在研究替地吡罗辛在马中以 4 mg/kg 体重 (bw) 进行单剂量静脉 (iv) 和皮下 (sc) 注射后的安全性和药代动力学 (PK) 特征。研究中总共使用了 12 匹健康的混合品种马。监测马的全身和局部不良反应，并在时间 (0) 和给药后 6、24 和 72 小时收集全血样本用于血液学和血浆生化分析。对于 PK 分析，在给药替地吡罗辛之前和之后的预定时间收集血液样品。使用超高效液相色谱-紫外检测法 (UHPLC-UV) 测定替地吡罗辛的血浆浓度。所有马都能耐受替地吡罗辛 iv 注射而没有表现出任何全身不良反应。然而，有 5 匹马 (41.7%) 的皮下注射部位出现了无痛的软肿胀。平均而言，替地吡罗辛达到最大血浆浓度（在皮下给药后 0.5 和 1.5 小时之间，C _max为 1257 ng/ml（几何平均值）（T _max）。全身清除率 (Cl)、基于终末相的表观分布容积(V _z ) 和稳态表观分布容积 (V _ss )的几何平均值为0.52 L/kg·h, 22分别为 L/kg 和 10.0 L/kg。本研究中收集的数据表明，替地吡罗辛可安全用于马匹，但需谨慎。