比阿培南与甲氨蝶呤、呋塞米在大鼠体内的药代动力学相互作用

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摘要目的初步考察比阿培南与甲氨蝶呤、呋塞米联合用药在大鼠体内的药代动力学相互作用。方法按照随机数字表法将15只雄性SD大鼠随机分为A、B和C组（每组5只）。A组尾静脉注射30 mg/kg比阿培南，B组尾静脉注射30 mg/kg比阿培南和3 mg/kg甲氨蝶呤，C组尾静脉注射30 mg/kg比阿培南和30 mg/kg呋塞米，于给药后不同时间点采集血浆和尿液，用HPLC法测定比阿培南浓度，并计算药代动力学参数。结果与A组比较，B组比阿培南在大鼠体内的血药浓度-时间曲线下面积显著降低，清除率和肾清除率显著增加（P ＜ 0.01）；C组比阿培南各药代动力学参数差异无统计学意义（P ＞ 0.05）。结论比阿培南和甲氨蝶呤、呋塞米联合用药后，甲氨蝶呤会导致比阿培南在大鼠体内的暴露量显著减少，清除率增加，而维拉帕米不会显著影响比阿培南在大鼠体内的药代动力学过程。

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	董婧1 李婷婷2 邱志霞3 陆燕1 李文艳1

关键词 ：比阿培南, 甲氨蝶呤, 呋塞米, 药代动力学相互作用, 高效液相色谱法

Abstract：Objective To investigate the pharmacokinetic interaction of Biapenem with Methotrexate and Furosemide in rats. Methods Fifteen male SD rats were randomly divided into group A, B and C (5 rats in each group) according to random number table method. Rats in group A were administered 30 mg/kg Biapenem by tail vein, rats in group B were administered 30 mg/kg Biapenem and 3 mg/kg Methotrexate by tail vein, and rats in group C were administered 30 mg/kg Biapenem and 30 mg/kg Furosemide by tail vein. Plasma and urine were collected at different time points after administration. The concentrations of Biapenem in rat plasma and urine were determined by HPLC and the pharmacokinetic parameters were calculated. Results Compared with group A, area under the curve of Biapenem decreased, CL and CLr of Biapenem increased significantly (P ＜ 0.01) in group B; compared with group A, there was no significant difference in pharmacokinetic parameters of Biapenem in group C (P ＞ 0.05). Conclusion When Biapenem is administered combined with Methotrexate and Furosemide, Methotrexate can significantly reduce the exposure and increase the clearance of Biapenem, while Furosemide cannot significantly affect the pharmacokinetic of Biapenem in rats.

Key words： Biapenem Methotrexate Furosemide Pharmacokinetic interaction High performance liquid chromatography

基金资助:国家自然科学基金资助项目（81803632）；
上海市浦东新区卫生系统优秀青年医学人才培养计划项目（PWRq2017-14）；
上海市浦东新区卫生和计划生育委员会临床药学重点学科项目（PWZxk2017-13）。

通讯作者: 李文艳（1971.6-），女，硕士，主任药师；研究方向：药物分析和临床药学。

作者简介: 董婧（1982.11-），女，博士；研究方向：药代动力学和临床药学。

引用本文:

董婧1 李婷婷2 邱志霞3 陆燕1 李文艳1. 比阿培南与甲氨蝶呤、呋塞米在大鼠体内的药代动力学相互作用[J]. 中国医药导报, 2019, 16(31): 22-25.
DONG Jing1 LI Tingting2 QIU Zhixia3 LU Yan1 LI Wenyan1. Pharmacokinetic interaction of Biapenem with Methotrexate and Furosemide in rats. 中国医药导报, 2019, 16(31): 22-25.

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