美罗培南对丙戊酸钠血药浓度和脑组织分布的影响

Effects of meropenem on sodium valproate:serum concentration and tissue distribution in brain

目的考察美罗培南对丙戊酸钠脑组织分布的影响。方法将100只健康昆明种雄性小鼠随机分为2组,即丙戊酸钠单用组及与美罗培南联用组(n=50)。单用组按100 mg/kg静脉给予丙戊酸钠;联用组在静脉给予美罗培南(100 mg/kg)10 min后,静脉给予丙戊酸钠(100 mg/kg)。运用HPLC-MS/MS法测定小鼠血浆和脑组织中丙戊酸钠的浓度。结果与单用组相比,联用组小鼠血浆中丙戊酸钠的浓度在给药后30、60、120、180 min时显著降低(P<0.05),且药物浓度—时间曲线下面积、平均驻留时间、半衰期均显著降低(P<0.05),而清除率显著升高(P<0.001);其脑组织中丙戊酸钠的浓度在给药后120 min时显著降低(P<0.05)。结论美罗培南与丙戊酸钠合用后能够降低丙戊酸钠的脑组织分布,从而影响其治疗作用,提示临床使用丙戊酸钠治疗癫痫的过程中需注意与美罗培南的药物相互作用问题。

Objective To investigate the effect of meropenem on brain tissues with sodium valproate.Methods One hundred male Kunming mice were randomly divided into two groups：sodium valproate group（n=50） and meropenem co-administration group（n=50）.Blood samples and brain tissues were collected at different times after intravenous injection of sodium valproate（100 mg/kg） alone and sodium valproate coadministration with meropenem（100 mg/kg） respectively.The concentration of sodium valproate in plasma and brain tissue was determined by liquid chromatography-mass spectrometry（LC-MS/MS）.Results Compared with the sodium valproate group,the concentration of sodium valproate in the meropenem co-administration group was significantly decreased at 30,60,120 and 180 min（P0.05） after the administration.AUC（0—3 h）,MRT（0—3 h）and t1/2were significantly decreased（P0.05） and CL significantly increased（P〈0.001）.The concentration of sodium valproate was significantly decreased in mice brain tissue at 120 min（P〈0.05）.Conclusion Concentration of sodium valproate in brain tissue can be reduced by meropenem,suggesting that meropenem should be avoided during the treatment of epilepsy by sodium valproate.