Yang Y, Yuan L, Li J, Muhammad I, Cheng P, Xiao T, Zhang X
Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, Faculty of Basic Veterinary Science, College of Veterinary Medicine, Northeast Agricultural University,600 Changjiang Road, Xiangfang District, Harbin, PR China.
Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, Faculty of Basic Veterinary Science, College of Veterinary Medicine, Northeast Agricultural University,600 Changjiang Road, Xiangfang District, Harbin, PR China; College of Veterinary Medicine, National Reference Laboratory of Veterinary Drug Residues (SCAU), South China Agricultural University, 510642 Guangzhou, China.
Vet J. 2019 Apr;246:27-34. doi: 10.1016/j.tvjl.2019.01.007. Epub 2019 Feb 1.
Tilmicosin (TMS) is a macrolide used extensively for pulmonary infections in clinical veterinary medicine. However, TMS has frequent administration and short elimination half-life. Therefore, tilmicosin-gelatine microspheres (TMS-GMS) were prepared by an emulsion-chemical cross-linking technique as a sustained-release formulation to extend drug half-life. The particle size distribution, in-vitro sustained-release properties, stability, and physical characteristics, as well as pharmacokinetic (PK) characteristics, were evaluated in rabbits. TMS-GMS were spherical in shape and had a mean diameter of 11.34±1.20μm; 95.65% of the microspheres varied in size from 5.0 to 25.0μm. Light and thermal stability tests indicated no significant changes in all observed indices. Importantly, compared to crude TMS, slower release of TMS from TMS-GMS was noted in drug release studies (in vitro). Pharmacokinetic (PK) characteristics were examined in the lung, liver, heart, kidney and muscle tissue of rabbits following IM injection of TMS-GMS or TMS-injection at a dose of 10mg/kg. The elimination half-life of TMS-GMS (59.21±0.21h) was longer than that of TMS-injection (38.56±0.13h) in the lung. The ratio of peak concentration (C) of TMS-GMS to TMS-injection was 2.19 (>1) in the lung, demonstrating the selectivity of TMS-GMS to target the lung compared to that of other tissues (C<1). Interestingly, the uptake value of TMS from TMS-GMS was 8.48 times higher in the lung than that for the TMS-injection, and was slightly higher than in the liver (1.85), heart (1.72), kidney (2.44) and muscle (2.79) tissues. TMS-GMS is a sustained-release formulation of TMS with potential to be used in veterinary clinical applications; possible benefits include lung-targeting and prolonged elimination half-life.
替米考星（TMS）是一种在临床兽医学中广泛用于治疗肺部感染的大环内酯类药物。然而，TMS给药频繁且消除半衰期短。因此，采用乳化-化学交联技术制备了替米考星-明胶微球（TMS-GMS）作为缓释制剂以延长药物半衰期。在兔体内评估了其粒径分布、体外缓释特性、稳定性、物理特性以及药代动力学（PK）特性。TMS-GMS呈球形，平均直径为11.34±1.20μm；95.65%的微球粒径在5.0至25.0μm之间。光照和热稳定性试验表明所有观察指标均无显著变化。重要的是，在药物释放研究（体外）中，与粗品TMS相比，TMS从TMS-GMS中的释放较慢。在兔肌肉注射10mg/kg剂量的TMS-GMS或TMS注射液后，对其肺、肝、心、肾和肌肉组织的药代动力学（PK）特性进行了研究。TMS-GMS在肺中的消除半衰期（59.21±0.21h）比TMS注射液（38.56±0.13h）长。TMS-GMS在肺中的峰浓度（C）与TMS注射液的比值为2.19（>1），表明与其他组织（C<1）相比，TMS-GMS对肺具有靶向选择性。有趣的是，TMS从TMS-GMS中的摄取值在肺中比TMS注射液高8.48倍，且略高于肝（1.85）、心（1.72）、肾（2.44）和肌肉（2.79）组织。TMS-GMS是TMS的一种缓释制剂，具有在兽医临床应用中的潜力；可能的益处包括肺靶向性和延长的消除半衰期。
