磺胺氯吡嗪钠-二甲氧苄啶可溶性粉在鸡体内的药代动力学研究
发布时间:2018-02-02 17:41
本文关键词: 球虫病 磺胺氯吡嗪钠 二甲氧苄啶 药代动力学 出处:《吉林大学》2017年硕士论文 论文类型:学位论文
【摘要】:磺胺氯吡嗪钠-二甲氧苄啶可溶性粉是一种新型抗球虫的复方制剂,它可以清除由柔嫩、布氏、毒害等多种艾美耳球虫引起的鸡的肠道感染,同时对家兔、羔羊的球虫病也具有很好的疗效。磺胺氯吡嗪钠主要作用于球虫的活性峰期的第二代裂殖体,而且它对第一代裂殖体也起到一些作用。它主要用于球虫的爆发短期使用。它还具有抗菌作用,也可以治疗禽霍乱及鸡伤寒。二甲氧苄啶作为一种磺胺药物的增效剂,也具有抗菌作用。目前来看,它是一种很有效的抗球虫病的复方制剂,在抗鸡球虫病的过程中起了很重要的作用。在世界范围内,它的使用很广,尤其在美国、欧洲等地。它便于储存、运输,但在国内还未上市。本研究建立高效液相的检测方法,并完成磺胺氯吡嗪钠-二甲氧苄啶可溶性粉在鸡体内的药代动力学研究。高效液相检测的色谱条件:色谱柱为大连伊力特色谱柱(250*4.6mm,5μm),填料为Hypersil ODS2,以0.1%甲酸水-乙腈(V/V=70:30)为流动相,流速为1m L/min,柱温为30℃,进样量为10μL。血浆样品使用乙腈做前处理后,制备待检测样品。磺胺氯吡嗪钠在0.1μg/m L—40μg/m L线性关系良好,二甲氧苄啶在0.1μg/m L—4μg/m L线性关系良好,该方法磺胺氯吡嗪钠、二甲氧苄啶的检测限均为0.05μg/m L,定量限为0.1μg/m L,该方法磺胺氯吡嗪钠的平均回收率为85.40%-97.13%,二甲氧苄啶的平均回收率为86%-97.36%,日内与日间变异系数均小于15%。且磺胺氯吡嗪钠、二甲氧苄啶在室温、三次反复冻融、-80℃冷冻条件下的稳定性均良好,符合生物样品的分析要求。并且该方法的灵敏度高,操作简便,可以用于磺胺氯吡嗪钠-二甲氧苄啶可溶性粉在鸡体内的药代动力学研究。药代动力学结果:通过给白羽肉鸡灌服低、中、高三种不同浓度的药物,使用DAS 3.0软件非房室模型对数据进行计算。两种药物的药代动力学参数如下:磺胺氯吡嗪钠的达峰时间T_(max)分别为7.833±1.337、9.333±1.303、9.667±1.155h;峰浓度C_(max)分别为10.16±0.922、17.457±0.663、26.905±2.154μg/m L;半衰期t_(1/2)分别为21.303±9.034、22.027±5.568、15.405±1.953h;药时曲线下面积AUC分别为288.534±43.743、568.828±56.072、859.145±90.379μg/m L*h。二甲氧苄啶的达峰时间T_(max)分别为4±0.853、4.333±1.435、4.333±1.435h;峰浓度C_(max)分别为0.261±0.045、0.37±0.065、0.66±0.059μg/m L;半衰期t_(1/2)分别为12.836±16.301、19.728±8.689、16.774±3.824h;药时曲线下面积AUC分别为2.013±0.867、5.383±1.882、11.212±3.7μg/m L*h。以上数据为磺胺氯吡嗪钠-二甲氧苄啶在临床的合理用药提供了理论依据。
[Abstract]:Sulfamethopyrazine-dimethoprim soluble powder is a new compound preparation against coccidiosis. It can eliminate the intestinal tract infection of chicken caused by Eimeria tenella, Brucella, toxicity and so on, and at the same time, it can treat rabbits. Sodium sulfamethopyrazine mainly acts on the second generation merozoite of coccidiosis in the peak stage of the activity of coccidiosis. And it also has some effect on the first generation of merozoites. It is mainly used for short-term use of coccidiosis. It also has antibacterial effect. Dimethoprim, as a synergist of sulfonamides, also has antimicrobial effect. At present, it is a very effective compound preparation against coccidiosis. It plays an important role in the fight against coccidiosis. It is widely used in the world, especially in the United States, Europe and other places. It is easy to store and transport. However, it has not been listed in China. In this study, a method for the detection of high performance liquid phase (HPLC) was established. The pharmacokinetics of sulfamethopyrazine-dimethoprim soluble powder in chicken was studied. The chromatographic conditions of high performance liquid chromatography (HPLC) were as follows: Dalian Eliot column 2504.6mm. The mobile phase was 0.1% formic acid water-acetonitrile V / V _ (70: 30) with flow rate of 1m L / min and column temperature of 30 鈩,
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