盐酸多西环素注射用长效非肠道制剂在犊牛体内的药代动力学研究

Pharmacokinetic study of an injectable long-acting parenteral formulation of doxycycline hyclate in calves.

作者信息

Vargas-Estrada D, Gracia-Mora J, Sumano H

机构信息

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

出版信息

Res Vet Sci. 2008 Jun;84(3):477-82. doi: 10.1016/j.rvsc.2007.07.003. Epub 2007 Aug 27.

DOI:10.1016/j.rvsc.2007.07.003

PMID:17720208

Abstract

Doxycycline hyclate (DOX-h) can be regarded as a time-dependant antibacterial. Hence, a parenteral long-acting formulation may be regarded as more pharmacologically sound. A poloxamer-based matrix was used to produce a long-acting injectable preparation (DOX-h-LA) and its serum concentrations vs. time profile investigated after its s.c. injection to calves. Serum concentrations profiles for such a prepartion were compared to the corresponding profiles obtained with an aqueous formulation of DOX-h injected either i.m. or i.v. in 10 calves in a crossover study at dose of 10mg/kg, with washout periods. DOX-h-LA showed the greatest values for bioavailability (602%); maximum serum concentration (C(max)) value was 1.99microg/mL with a time to reach C(max) (T(max)) of 25h and an elimination half-life of 40.81h. Considering minimum effective serum concentration of 0.5microg/mL a dose-interval of 80h can be achieved for DOX-h-LA, and only 9.7h and 17h after the i.v. or i.m. administration of DOX-h, respectively.

摘要

盐酸多西环素（DOX-h）可被视为一种时间依赖性抗菌药物。因此，肠胃外长效制剂在药理学上可能更合理。一种基于泊洛沙姆的基质被用于制备长效注射制剂（DOX-h-LA），并在对犊牛进行皮下注射后研究其血清浓度随时间的变化情况。在一项交叉研究中，将10头犊牛以10mg/kg的剂量分别静脉注射和肌肉注射盐酸多西环素水性制剂，并设置洗脱期，然后将该制剂的血清浓度曲线与上述制剂的相应曲线进行比较。DOX-h-LA的生物利用度最高（602%）；最大血清浓度（C(max)）值为1.99μg/mL，达到C(max)的时间（T(max)）为25小时，消除半衰期为40.81小时。考虑到最低有效血清浓度为0.5μg/mL，DOX-h-LA的给药间隔可达80小时，而盐酸多西环素静脉注射和肌肉注射后分别仅为9.7小时和17小时。