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阿莫西林在 3 种水消毒剂影响下的体外抗菌活性及其在肉鸡中的口服生物利用度。

Antibacterial activity of amoxicillin in vitro and its oral bioavailability in broiler chickens under the influence of 3 water sanitizers.

机构信息

Department of Physiology and Pharmacology, School of Veterinary Medicine, National Autonomous University of Mexico, Av. Universidad 3000, Coyoacán, Mexico City 04510, Mexico.

Department of Avian Medicine, School of Veterinary Medicine, National Autonomous University of Mexico, Av. Universidad 3000, Coyoacán, Mexico City 04510, Mexico.

出版信息

Poult Sci. 2018 Jul 1;97(7):2391-2399. doi: 10.3382/ps/pey114.

Abstract

The interaction of 3 water sanitizers (sodium hypochlorite, iodine-polyvinylpyrrolidone, and citrate) utilized in poultry production on antibacterial activity and bioavailability of amoxicillin trihydrate (AMX) were studied. Sanitizers were mixed with AMX in prepared water, the resulting substances were regarded as amoxicillin-sanitizer products (ASP). First, the in vitro antibacterial activity of each ASP was compared to that of AMX. Then, pharmacokinetics (PK) of ASP and AMX diluted in prepared water, were carried out in broiler-chickens. Amoxicillin or ASP (20 mg/kg) from different concentrations of sanitizers was directly placed into the chicken's crop and blood samples were taken. Basic PK parameters were obtained. Serum activity/concentrations of AMX were assessed by agar diffusion and corroborated with high performance liquid chromatography. Results show that ASP of AMX/sodium hypochlorite decrease both, the antimicrobial activity of in vitro AMX and its relative bioavailability (Fr) assessed with the maximum serum concentration (Cmax), the area under the concentration-time curve, and the mean residence time (MRT) (3.80 μg/mL, 2.70 μg/mL·h, and 0.59 h, respectively), compared to the AMX administered alone (12.54 μg/mL, 44.02 μg/mL·h, and MRT 2.78 h). ASP from amoxicillin/ionophore, reduced the Cmax (10.62 μg/mL), Fr (94.67%), and MRT (2.07 h), at the highest tested concentrations. In contrast, the 2 highest concentrations of the citrate sanitizer increased the Cmax (15.07 and 15.47 μg/mL), Fr (119 and 132%), and MRT (3.32 and 4.06 h) and their in vitro antimicrobial activity. Interactions between the tested water sanitizers and AMX modify the Cmax, Fr, MRT of the latter, altering the PK/pharmacodymanic ratios for a time-dependent antibiotic. Results also reveal that the use of amoxicillin trihydrate administered through the drinking water does not meet the required PK/pharmacodymanic ratios. Thus, it is here postulated that this antibiotic should be administered at least twice a day and that its interaction with water sanitizers should be considered.

摘要

研究了在禽类生产中使用的 3 种水消毒剂(次氯酸钠、碘-聚乙烯吡咯烷酮和柠檬酸盐)对阿莫西林三水合物(AMX)的抗菌活性和生物利用度的相互作用。消毒剂与 AMX 混合在配制水中,所得物质被视为阿莫西林-消毒剂产品(ASP)。首先,比较了每种 ASP 的体外抗菌活性与 AMX 的抗菌活性。然后,在肉鸡中进行了稀释在配制水中的 ASP 和 AMX 的药代动力学(PK)研究。从不同浓度的消毒剂中直接将阿莫西林或 ASP(20mg/kg)放入鸡的嗉囊中,并采集血样。获得基本 PK 参数。通过琼脂扩散评估 AMX 的血清活性/浓度,并与高效液相色谱法相吻合。结果表明,ASP 的 AMX/次氯酸钠降低了体外 AMX 的抗菌活性及其相对生物利用度(Fr),以最大血清浓度(Cmax)、浓度-时间曲线下面积和平均驻留时间(MRT)评估,与单独使用 AMX(12.54μg/mL、44.02μg/mL·h 和 MRT 2.78h)相比。ASP 的 AMX/离子载体降低了 Cmax(10.62μg/mL)、Fr(94.67%)和 MRT(2.07h),在测试的最高浓度下。相比之下,2 种最高浓度的柠檬酸消毒剂增加了 Cmax(15.07 和 15.47μg/mL)、Fr(119 和 132%)和 MRT(3.32 和 4.06h)及其体外抗菌活性。测试的水消毒剂与 AMX 之间的相互作用改变了 AMX 的 Cmax、Fr、MRT,改变了时间依赖性抗生素的 PK/药效动力学比值。结果还表明,通过饮用水给予阿莫西林三水合物不符合所需的 PK/药效动力学比值。因此,这里假设该抗生素应至少每天给药 2 次,并应考虑其与水消毒剂的相互作用。

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