一种新型阿莫西林-丙磺舒拼合物在小鼠体内的药代动力学  

Pharmacokinetics of a novel amoxicillin probenecid hybrid molecules in mice

作　　者：李晗 李艳芹[1] 李仲林 陈良柱 方炳虎[1,2] LI Han;LI Yan-qin;LI Zhong-lin;CHEN Liang-zhu;FANG Bing-hu(National Reference Laboratory of Veterinary Drug Residues,College of Veterinary Medicine,South China Agricultural University,Guangzhou 510642 China;Guangdong Wens Dahuanong Biotechnology Co.,Ltd.,Yunfu,Guangdong 527300 China)

机构地区：[1]华南农业大学兽医学院,广东广州510642 [2]广东温氏大华农生物科技有限公司,广东云浮527300

出　　处：《中国兽医学报》2020年第3期608-612,共5页Chinese Journal of Veterinary Science

基　　金：国家自然科学基金资助项目(31672601)。

摘　　要：以阿莫西林、阿莫西林/丙磺舒联合用药为对照,研究一种新型阿莫西林-丙磺舒拼合物在小鼠体内的比较药代动力学。采用超高效液相色谱-串联质谱(UPLC-MS/MS)法测定小鼠血浆中阿莫西林和丙磺舒的浓度,WinNonlin(Version5.2.1)软件计算药动学参数。阿莫西林、阿莫西林/丙磺舒联合用药及拼合物在小鼠体内的达峰浓度(Cmax)分别为(3.31±0.40),(4.47±0.36),(4.50±0.29)mg/L,达峰时间(Tmax)分别为(1.08±0.21),(1.42±0.20),(1.58±0.32)h,药物半衰期t1/2ke分别为(1.04±0.21),(1.49±0.50),(1.77±0.23)h,AUClast分别为(5.76±0.60),(10.34±0.94),(11.41±0.75)mg·h/L,MRTlast分别为(1.81±0.11),(2.59±0.47),(2.64±0.24)h,拼合物的相对生物利用度F为110.35%(与阿莫西林/丙磺舒联合用药相比)。结果表明,拼合物组小鼠血浆中阿莫西林的Cmax、AUClast及MRTlast比阿莫西林组有显著的提高(P<0.01)。与阿莫西林/丙磺舒联合用药比较,拼合物实验组半衰期t1/2ke和AUClast也有较明显提高(0.01<P<0.05),其长效作用更显著。The pharmacokinetics of a novel amoxicillin/probenecid hybrid molecules was evaluated after a single oral administration in mice.The pharmacokinetic characteristics of amoxicillin/probenecid hybrid molecules were compared with single amoxicillin and the amoxicillin/probenecid combination.The Ultra-high pressure liquid chromatography tandem mass spectrometry method(UPLC-MS/MS)was used to determine content of amoxicillin in mice.In the amoxicillin group,the amoxicillin/probenecid combination group and the hybrid molecules group,the peak plasma concentrations(Cmax)of amoxicillin were(3.31±0.40),(4.47±0.29)and(4.50±0.29)mg/L,respectively after oral administration.The peak times(Tmax)were(1.08±0.21),(1.42±0.20)and(1.58±0.32)hours,respectively.Mean elimination half-lifes(t1/2ke)were(1.04±0.21),(1.49±0.50)and(1.77±0.23)h,respectively.Area under plasma concentration curves(AUClast)were(5.76±0.60),(10.34±0.94)and(11.41±0.75)mg·h/L,respectively.Mean residence times(MRTlast)were(1.81±0.11),(2.59±0.47)and(2.46±0.24)h,respectively.The relative bioavailability(F)of hybrid molecules to the amoxicillin/probenecid combination was 110.35%.The results showed the Cmax,AUClastand MRTlast of amoxicillin in the plasma of the mice in the hybrid molecules group were significantly higher than those in the amoxicillin group(P<0.01).Compared with the amoxicillin/probenecid conbination group,the t1/2keand AUClastof the hybrid molecules group was also significantly increased(0.01<P<0.05),indicating that its long-acting effect was more notable.

关 键 词：拼合物 阿莫西林 丙磺舒 药代动力学 

分 类 号：S859.7[农业科学—临床兽医学]