兔体内美罗培南对丙戊酸钠稳态血药浓度及药动学的影响

Effect of meropenem on pharmacokinetics of sodium valproate at steady state in rabbits

目的:观察兔注射美罗培南前后对稳态时丙戊酸钠(sodium valproate,SVPA)血药浓度及药动学参数的影响。方法:采用高效液相色谱法测定单用组(Ⅰ期)和合用组(Ⅱ期)兔给药后不同时间点SVPA的血药浓度。血药浓度-时间数据用非线性程序WINNONL IN拟合,求得SVPA的药动学参数。结果:合并用药后(Ⅱ期)峰值时间内SVPA血药浓度(0.5,1.5 h)比单独应用SVPA(Ⅰ期)的浓度显著降低,二者有显著性差异(P<0.05)。合并用药后(Ⅱ期)SVPA的消除半衰期(t1/2β)低于单用者(Ⅰ期),二者有显著性差异(P<0.05)。合并用药后血浓度达峰时间推迟,但与单用组比较其差异无统计学意义,其他药动学参数无显著性差异。结论:美罗培南可以使SVPA的峰浓度显著降低,而使其t1/2延长,两药合用时应注意监测SVPA的血药浓度,及时调整给药剂量。

OBJECTIVE To observe the effects of inject meropenem on serum concentrations at steady state and its pharmacokinetics of sodium valproate（SVPA） in New Zealand rabbits.METHODS After oral administration of SVPA or SVPA combined with meropenem,the plasma drug levels were measured by high-performance liquid chromatography（HPLC）.The plasma concentration-time data were accessed by non-linear program（WINNONL IN） and the pharmacokinetic parameters were obtained.RESULTS There was significant decreasing of SVPA blood concentration at peak value time（0.5 h and 1.5 h） inⅡstage（P〈0.05）.Theeliminate（t1/2β） of SVPA inⅡstage was lower than that of Ⅰstage（P〈0.05）.The other pharmacokinetics parameters were not changed significantly between two stages.CONCLUSION There was significant decreasing of SVPA blood when oral meropenem in New Zealand rabbits.They can be taken simultaneously,but the concentration of SVPA theohylline in plasma should be monitored