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皮下注射长效制剂后肉鸡血清和组织中的强力霉素浓度。

Serum and tissue concentrations of doxycycline in broilers after the sub-cutaneous injection of a long-acting formulation.

机构信息

Departamento de Fisiología y Farmacología, Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Av. Universidad 3000, Delegación Coyoacán, Ciudad de México C.P. 04510.

出版信息

Br Poult Sci. 2012;53(3):366-73. doi: 10.1080/00071668.2012.701004.

Abstract
  1. The antibacterial agent doxycycline hyclate (Dox) is usually administered to broilers in drinking water or as a feed supplement. Parenteral injection is not the usual route for administration, so a long-acting formulation (Dox-LA) was tested to evaluate if serum concentrations can achieve the pharmacokinetic/pharmacodynamic (PK/PD) ratios regarded as adequate for the drug. 2. A poloxamer-based matrix was used to provide Dox-LA. Serum and tissue concentrations of Dox vs time were determined in two day-old broilers after subcutaneous (SC) injection of Dox-LA or oral administration of a single bolus of aqueous Dox (Dox-PO), at a dose of 20 mg/kg. Weight gain, feed conversion rate, haematological variables, aspartate aminotransferase and alanine aminotransferase activities, blood urea and creatinine were determined and compared for Dox-LA with Dox-PO and non-medicated controls. 3. Dox-LA had a high relative bioavailability (1200%). Maximum serum concentrations were not statistically different (5·1 ± 1·1 µg/ml for Dox-LA and 6·1 ± 1.4 µg/ml for Dox-PO), but half-life of Dox-LA was much greater than the value obtained for Dox-PO (73·0 ± 0·9 h and 2·0 ± 0·02 h, respectively). Tissue concentrations were higher, and stayed higher for longer periods in the Dox-LA group. 4. In conclusion, considering the minimum effective serum concentration against Mycoplasma spp is 0·5 µg/ml, a dose-interval of 180 h can be achieved with Dox-LA, but only for 24 h after Dox-PO. Better PK/PD ratios for Dox-LA should result in improved clinical outcomes compared with Dox-PO.
摘要
  1. 盐酸多西环素(Dox)是一种常用的抗菌剂,通常通过饮水或饲料添加剂的方式给肉鸡给药。由于不是常规的给药途径,因此我们测试了一种长效制剂(Dox-LA),以评估其血清浓度是否能达到被认为对该药物有效的药代动力学/药效学(PK/PD)比值。

  2. 我们使用泊洛沙姆基质来提供 Dox-LA。在 2 日龄肉鸡中,通过皮下(SC)注射 Dox-LA 或口服单次水混悬 Dox(Dox-PO)(剂量为 20 mg/kg),检测 Dox-LA 或 Dox-PO 给药后血清和组织中 Dox 随时间的浓度变化。比较 Dox-LA 与 Dox-PO 及未用药对照组的体重增加、饲料转化率、血液学变量、天门冬氨酸氨基转移酶和丙氨酸氨基转移酶活性、血尿素和肌酐。

  3. Dox-LA 具有较高的相对生物利用度(1200%)。最大血清浓度无统计学差异(Dox-LA 为 5.1±1.1 µg/ml,Dox-PO 为 6.1±1.4 µg/ml),但 Dox-LA 的半衰期明显长于 Dox-PO(分别为 73.0±0.9 h 和 2.0±0.02 h)。Dox-LA 组的组织浓度更高,且维持更长时间。

  4. 综上所述,考虑到针对支原体属的最低有效血清浓度为 0.5 µg/ml,Dox-LA 可实现 180 h 的给药间隔,但 Dox-PO 仅能维持 24 h。与 Dox-PO 相比,Dox-LA 具有更好的 PK/PD 比值,应能带来更好的临床效果。

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