阿莫西林和舒巴坦被广泛用于动物性食品复合。阿莫西林-舒巴坦杂化分子是阿莫西林和舒巴坦与亚甲基基团连接而成的双酯化合物,具有良好的应用前景。然而,这些杂种分子在动物中的残留消除模式需要探索。在本研究中,阿莫西林-舒巴坦混合分子(AS组)和阿莫西林和舒巴坦的混合物(混合物组)通过管饲法给予大鼠,以及阿莫西林主要代谢产物的水平,amoxicilloicacid,阿莫西林二酮哌嗪,和舒巴坦的测定采用UPLC-MS/MS。肝脏中主要代谢物的残留消除模式,肾,尿液,比较AS组和混合组大鼠的粪便。结果表明,阿莫西林的总量,amoxicilloicacid,阿莫西林二酮哌嗪,AS组和混合组肝肾标本中舒巴坦的最高浓度出现在停药后1h。停药后1小时至12小时之间,阿莫西林的总量,amoxicilloicacid,和阿莫西林二酮哌嗪在两个组织中迅速下降,AS组的消除半衰期明显高于混合组(p<0.05);舒巴坦的残留量也迅速下降,消除半衰期无显著差异(p>0.05)。在72小时的尿液样本中,AS组和混合组的总排泄率分别为60.61±2.13%和62.62±1.73%,分别。AS组和混合组的粪便样本(72h)的总排泄率分别为9.54±0.26%和10.60±0.24%,分别。这些结果表明,阿莫西林的总量,amoxicilloicacid,与混合组相比,AS组的肝脏和肾脏中阿莫西林二酮哌嗪的消除速度更慢,两组通过尿液和粪便的排泄率基本相同。本研究确定的杂合分子在大鼠体内的残留消除规律,为杂合分子的深入开发和应用提供了理论依据,以及类似药物的开发指南。
Amoxicillin and
sulbactam are widely used in animal food compounding. Amoxicillin-
sulbactam hybrid molecules are bicester compounds made by linking amoxicillin and
sulbactam with methylene groups and have good application prospects. However, the residual elimination pattern of these hybrid molecules in animals needs to be explored. In the present study, the amoxicillin-
sulbactam hybrid molecule (AS group) and a mixture of amoxicillin and
sulbactam (mixture group) were administered to rats by gavage, and the levels of the major metabolites of amoxicillin, amoxicilloic acid, amoxicillin diketopiperazine, and
sulbactam were determined by UPLC-MS/MS. The residue elimination patterns of the major metabolites in the liver, kidney, urine, and feces of rats in the AS group and the mixture group were compared. The results showed that the total amount of amoxicillin, amoxicilloic acid, amoxicillin diketopiperazine, and the highest concentration of sulbactam in the liver and kidney samples of the AS group and the mixture group appeared at 1 h after drug withdrawal. Between 1 h and 12 h post discontinuation, the total amount of amoxicillin, amoxicilloic acid, and amoxicillin diketopiperazine in the two tissues decreased rapidly, and the elimination half-life of the AS group was significantly higher than that in the mixture group (p < 0.05); the residual amount of sulbactam also decreased rapidly, and the elimination half-life was not significantly different (p > 0.05). In 72 h urine samples, the total excretion rates were 60.61 ± 2.13% and 62.62 ± 1.73% in the AS group and mixture group, respectively. The total excretion rates of fecal samples (at 72 h) for the AS group and mixture group were 9.54 ± 0.26% and 10.60 ± 0.24%, respectively. These results showed that the total quantity of amoxicillin, amoxicilloic acid, and amoxicillin diketopiperazine was eliminated more slowly in the liver and kidney of the AS group than those of the mixture group and that the excretion rate through urine and feces was essentially the same for both groups. The residual elimination pattern of the hybrid molecule in rats determined in this study provides a theoretical basis for the in-depth development and application of hybrid molecules, as well as guidelines for the development of similar drugs.