The objective of this study was to determine the pharmacokinetics of tildipirosin in rabbits after a single intravenous (i.v.) and intramuscular (i.m.) injection at a dose of 4 mg/kg. Twelve white New Zealand rabbits were assigned to a randomized, parallel trial design. Blood samples were collected prior to administration and up to 14 days postadministration. Plasma concentrations of tildipirosin were quantified using a validated ultra‐high‐performance liquid chromatography tandem mass spectrometry (UPLC‐MS/MS) method. The pharmacokinetic parameters were calculated using a noncompartmental model in WinNonlin 5.2 software. Following i.v. and i.m. administration, the elimination half‐life (T_1/2λ) was 81.17 ± 9.28 and 96.68 ± 15.37 hr, respectively, and the mean residence time (MRT_last) was 65.44 ± 10.89 and 67.06 ± 10.49 hr, respectively. After i.v. injection, the plasma clearance rate (Cl) and volume of distribution at steady state (V_dss) were 0.28 ± 0.10 L kg^‐1 h⁻¹ and 17.78 ± 5.15 L/kg, respectively. The maximum plasma concentration (C_max) and time to reach maximum plasma concentration (T_max) after i.m. administration were 836.2 ± 117.9 ng/ml and 0.33 ± 0.17 hr, respectively. The absolute bioavailability of i.m. administration was 105.4%. Tildipirosin shows favorable pharmacokinetic characteristics in rabbits, with fast absorption, extensive distribution, and high bioavailability. These findings suggest that tildipirosin might be a potential drug for the prevention and treatment of respiratory diseases in rabbits.

中文翻译：

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单剂量静脉和肌肉内给药后，替地吡辛在家兔的药代动力学和生物利用度。

这项研究的目的是确定在剂量为4 mg / kg的单次静脉内（iv）和肌肉内（im）注射后，替地吡辛在兔体内的药代动力学。将十二只新西兰白兔分配到随机平行试验设计中。在给药前和给药后最多14天收集血样。使用经过验证的超高效液相色谱串联质谱法（UPLC-MS / MS）定量对替地吡辛的血浆浓度。使用WinNonlin 5.2软件中的非房室模型计算药代动力学参数。静脉和肌肉注射后，消除半衰期（T _{1 /2λ}）分别为81.17±9.28和96.68±15.37 hr，并且平均停留时间（_最后一次MRT）分别为65.44±10.89和67.06±10.49小时。静脉注射后，血浆清除率（Cl）和稳态时的分布体积（V _dss）分别为0.28±0.10 L kg ^-1  h ^-1和17.78±5.15 L / kg。最大血浆浓度（C _max）和达到最大血浆浓度的时间（T _maxim给药后）分别为836.2±117.9 ng / ml和0.33±0.17 hr。即时给药的绝对生物利用度为105.4％。Tildipirosin在兔中显示出良好的药代动力学特征，具有吸收快，分布广泛和高生物利用度的特点。这些发现表明，替地吡辛可能是预防和治疗家兔呼吸系统疾病的潜在药物。