Tildipirosin is a semi‐synthetic macrolide antibiotic commonly used in cattle and swine to treat bacterial pneumonia. The objective of this study was to investigate the pharmacokinetic profile of tildipirosin after a single intravenous (i.v.) and subcutaneous (s.c.) administration in healthy lambs. Eighteen lambs were randomly divided into three groups (n = 6 each). Lambs received a single s.c. dose of tildipirosin at 4 and 6 mg/kg b.w. in group 1 and 2, respectively. Lambs in group 3 received a single i.v. dose of tildipirosin at 4 mg/kg b.w. Blood samples were collected at 0, 0.5, 0.75, 1.5, 2, 3, 4, 6, 8, 10, 24, 36, 48 hr, and every 24 hr to day 21, and thereafter at day 28 posttildipirosin administration. The plasma concentrations of tildipirosin were determined using high‐performance liquid chromatography with tandem mass spectrometry detection (LC⁄MS⁄MS). All lambs appeared to tolerate both the intravenous and subcutaneous injection of tildipirosin. Following i.v. administration, the elimination half‐life (T_1/2), mean residence time (MRT), volume of distribution (Vd/F), and total body clearance (Cl/F) were 119.6 ± 9.0 hr, 281.9 ± 25.7 hr, 521.1 ± 107.2 L, and 2.9 ± 0.5 L/hr, respectively. No significant differences in C_max (657.0 ± 142.8 and 754.6 ± 227.1 ng/ml), T_max (1.21 ± 0.38 and 1.35 ± 0.44 hr), T_1/2 (144 ± 17.5, 156.5 ± 33.4 hr), and MRT (262.0 ± 30.2 and 250.6 ± 54.5 hr) were found in tildipirosin after s.c. dosing at 4 and 6 mg/kg b.w., respectively. The absolute bioavailability (F) of tildipirosin was 71.5% and 75.3% after s.c. administration of 4 and 6 mg/kg b.w., respectively. In conclusion, tildipirosin was rapidly absorbed and slowly eliminated after a single s.c. administration in healthy lambs. Tildipirosin could be used for the treatment and prevention of respiratory bacterial infections in sheep. However, further in vitro and in vivo studies to determine the efficacy and safety are warranted. To our knowledge, this is the first study to determine the tildipirosin pharmacokinetic parameters in sheep plasma.

中文翻译：

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替地吡罗辛在绵羊静脉和皮下给药后的药代动力学和生物利用度。

替地吡菌素是一种半合成的大环内酯类抗生素，常用于牛和猪治疗细菌性肺炎。本研究的目的是调查健康羔羊单次静脉内 (iv) 和皮下 (sc) 给药后替地吡罗辛的药代动力学特征。十八只羊羔被随机分成三组（每组 n = 6）。在第 1 组和第 2 组中，羔羊分别皮下注射 4 和 6 毫克/千克体重的替地吡罗辛。第 3 组的羔羊接受 4 mg/kg bw 的单次静脉注射替地吡罗辛 在 0、0.5、0.75、1.5、2、3、4、6、8、10、24、36、48 小时和每 24 小时至第 21 天一次，此后在给药后第 28 天。替地吡罗辛的血浆浓度使用串联质谱检测 (LC⁄MS⁄MS) 的高效液相色谱法测定。所有羔羊似乎都能耐受替地吡罗辛的静脉内和皮下注射。静脉给药后，消除半衰期（T_1/2 )、平均停留时间 (MRT)、分布容积 (Vd/F) 和全身清除率 (Cl/F) 分别为 119.6 ± 9.0 小时、281.9 ± 25.7 小时、521.1 ± 107.2 L 和 2.9 ± 0.5升/小时，分别。C _max (657.0 ± 142.8 和 754.6 ± 227.1 ng/ml)、T _max (1.21 ± 0.38 和 1.35 ± 0.44 hr)、T _1/2没有显着差异（144 ± 17.5、156.5 ± 33.4 小时）和 MRT（262.0 ± 30.2 和 250.6 ± 54.5 小时）分别以 4 和 6 毫克/千克体重皮下给药后在替地吡罗辛中发现。在皮下给药 4 和 6 毫克/千克体重后，替地吡罗辛的绝对生物利用度 (F) 分别为 71.5% 和 75.3%。总之，替地吡罗辛在健康羔羊中单次皮下给药后被迅速吸收并缓慢消除。替地吡菌素可用于治疗和预防绵羊呼吸道细菌感染。然而，需要进一步的体外和体内研究来确定疗效和安全性。据我们所知，这是第一项确定绵羊血浆中替地吡罗辛药代动力学参数的研究。