普萘洛尔对盐酸二甲双胍大鼠肾排泄的影响

Effects of co-administration of propranolol on the renal excretion of metformin hydrochloride in rats

目的:考察普萘洛尔对盐酸二甲双胍肾排泄的影响。方法:20只健康Wistar雄性大鼠随机分为2组,一组尾静脉注射盐酸二甲双胍和普萘洛尔,另一组注射盐酸二甲双胍,于给药后收集各时间段(0～2,2～4,4～6,6～8,8～10,10～12,12～24 h)的尿液样品。用高效液相色谱法测定二甲双胍尿药浓度,用DAS 2.0软件计算二甲双胍的药动学参数后对数据进行分析。结果:联合用药组的药动学参数t1/2,Ke[(2.8±0.4)h,(0.25±0.58)h-1]较二甲双胍组[(2.11±0.30)h,(0.34±0.45)h-1]存在统计学差异(P<0.05),但总尿排量较二甲双胍组无显著性差异(P>0.05)。结论:普萘洛尔对健康Wistar雄鼠盐酸二甲双胍的肾排泄速率有显著影响,可能与其竞争性抑制了肾脏rOCT2有关。

OBJECTIVE To study the effects of co-administration of propranolol on the renal excretion of metformin hydro- chloride in rats. METHODS 20 young male rats were randomly divided into 2 equal groups. After the rats of the co-administra- tion group treated with both propranolol and metformin hydrochloride, metformin hydrochloride group were treated only with metformin hydrochloride via tail vein injection, the urine samples were collected in 0 - 2,2 - 4,4 - 6,6 - 8,8 - 10,10 - 12 and 12 - 24 h. The concentrations of metformin hydrochloride in urine were determined by high performance liquid chromatography. According to the concentration of urine, the software of DAS 2. 0 was used to calculate the pharmacokinetic parameters. RE- SULTS The significantly changed pharmacokinetic parameters of the metformin group and the testing group （P〈0. 05） in rats：t1/2 were （2.8 ± 0.4） and （2. 11 ± 0. 30） h,respectively;Ke were （0. 25 ± 0. 58） and （0. 34 ± 0.45） h^-1 respectively;while the total urine discharge of metformin was not significantly changed （P〉0.05）. CONCLUSION Propranolol had significanl effect on the renal excretion process of metformin hydrochloride in rats; the possible reason was that propranolol may competi- tively inhibit renal rOCT2 in rats.