Department of Pharmacology, Faculty of Veterinary Medicine, Aswan University, Aswan, Egypt.
Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.
BMC Vet Res. 2024 Jun 8;20(1):251. doi: 10.1186/s12917-024-04089-6.
The study was conducted to evaluate the influence of theophylline pre-treatment on serum pharmacokinetics and milk elimination of tylosin following single intramuscular (IM) administrations in lactating goats.
In a cross-over study, tylosin was injected via intramuscular (IM) at a single dose of 15 mg/kg b.wt. After a one-month washout period goats received theophylline at a daily IM dose of 2 mg/kg b.wt. for seven consecutive days then tylosin was injected IM dose of 15 mg/kg b.wt. two hours after the last theophylline dosing. Blood samples were collected before and at 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, and 24 h post-injection. Samples were left to clot and then centrifuged to yield serum. Milk samples were collected before and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 48, and 72 h post-injection from each goat by hand milking. Tylosin serum concentrations were determined by high-performance liquid chromatography (HPLC). Tylosin concentrations versus time were analyzed by a noncompartmental method. Tylosin C significantly declined from 1.73 ± 0.10 to 1.01 ± 0.11 µg/ml, and attained T values of 2 and 1 h, respectively in theophylline-pretreated goats. Moreover, theophylline pretreatment significantly shortened the elimination half-life (t) from 6.94 to 1.98 h, t from 0.62 to 0.36 h and the mean residence time (MRT) from 8.02 to 4.31 h, also Vz/F and AUCs decreased from 11.91 to 7.70 L/kg and from 12.64 to 4.57 µgh/ml, respectively, consequently, theophylline enhanced the clearance (Cl/F) of tylosin from the body. Similarly, tylosin milk concentrations were significantly lower in theophylline-pretreated goats than in goats that received tylosin alone and were detected up to 24 and 72 h in both groups, respectively. Moreover, the t and AUCs were significantly decreased from 14.68 ± 1.97 to 4.72 ± 0.48 h, and from 181 to 67.20 µgh/ml, respectively.
The withdrawal period for tylosin in goat milk is at least 72 h. Theophylline pretreatment significantly decreases serum and milk tylosin concentrations to subtherapeutic levels, which could have serious clinical consequences such as failure of therapy. This means that after administering tylosin to goats, milk from these animals should not be consumed for at least 96 h to ensure that the milk is free from residues of the antibiotic.
本研究旨在评估茶碱预处理对泌乳山羊单次肌肉注射（IM）泰乐菌素后血清药代动力学和乳汁消除的影响。
在一项交叉研究中，泰乐菌素以 15mg/kg b.wt 的单剂量 IM 给药。在一个月的洗脱期后，山羊接受每日 IM 剂量 2mg/kg b.wt 的茶碱治疗，连续 7 天，然后在最后一次茶碱给药后 2 小时 IM 注射 15mg/kg b.wt 的泰乐菌素。在注射前和注射后 0.25、0.5、0.75、1、2、4、6、8、10、12 和 24 小时采集血样。血样放置凝固后离心以获得血清。从每只山羊中手动挤奶，在注射前和注射后 0.5、1、2、4、6、8、10、12、24、48 和 72 小时采集乳汁样本。通过高效液相色谱法（HPLC）测定泰乐菌素血清浓度。采用非房室法分析泰乐菌素浓度与时间的关系。在茶碱预处理的山羊中，泰乐菌素 C 浓度从 1.73±0.10μg/ml 显著下降至 1.01±0.11μg/ml，并分别达到 2 和 1 小时的 T 值。此外，茶碱预处理显著缩短消除半衰期（t）从 6.94 小时至 1.98 小时，t 从 0.62 小时至 0.36 小时，平均驻留时间（MRT）从 8.02 小时至 4.31 小时，Vz/F 和 AUCs 分别从 11.91L/kg 降至 7.70L/kg 和从 12.64μgh/ml 降至 4.57μgh/ml，因此，茶碱增强了泰乐菌素从体内的清除（Cl/F）。同样，在接受茶碱预处理的山羊中，泰乐菌素乳汁浓度明显低于单独接受泰乐菌素的山羊，两组分别在 24 小时和 72 小时检测到泰乐菌素。此外，t 和 AUCs 分别从 14.68±1.97 小时显著下降至 4.72±0.48 小时和从 181 微克h/ml 显著下降至 67.20 微克h/ml。
在山羊乳中泰乐菌素的停药期至少为 72 小时。茶碱预处理可显著降低血清和乳汁中泰乐菌素的浓度至治疗性水平以下，这可能会产生严重的临床后果，如治疗失败。这意味着在给山羊注射泰乐菌素后，这些动物的乳汁应至少在 96 小时内不被消耗，以确保乳汁中没有抗生素残留。
