环丙沙星对苯妥英钠药动学的影响

Effect of ciprofloxacin on phenytoin pharmacokinetics in rabbits

目的 :研究环丙沙星对苯妥英血药浓度及药动学参数的影响。方法 :应用紫外分光光度法测定家兔喂服环丙沙星 (2 5mg·kg-1)前及 1周后单剂量静注苯妥英钠 (10mg·kg-1)的经时血药浓度 ,以“3P87”药动学程序拟合药动学参数。结果 :合用环丙沙星后 ,苯妥英血药浓度明显下降 (P <0 .0 5 ) ,AUC由合并用药前 (6 6 39.0± 893.9)mg·L-1·min-1降为 (42 0 0 .7±874 .4 )mg·L-1·min-1,消除半衰期 (T1/ 2 )缩短 32 .8% (P <0 .0 5 ) ,消除速度常数 (Ke)和清除率 (CL)分别比原来增加 14 4 %和 133% (P <0 .0 1) ,Vd 无显著影响 (P >0 .0 5 )。结论 :合用环丙沙星后可引起苯妥英血药浓度明显下降 ,AUC、T1/ 2 降低 ,Ke、CL升高。提示合用环丙沙星后可加快苯妥英的体内代谢。

OBJECTIVE To study the effect of ciprofloxacin(CPFX) on phenytoin sodium (PHT) serum concentrations and pharmacokinetics in rabbits.METHODS Eight rabbits were given with PHT (10 mg·kg -1 ,iv) and the serum concentration of PHT in different time was determined by UV. After a week, CPFX was administered for seven days. At the eighth day, PHT was concurrently administered. Serum concentration of PHT was determined by same methods.Results and conclusion The metabolism of PHT was fit to one open compartment model. The apparent clearance (CL)? half life time( T 1/2 )? area under concentration cure (AUC) and elimination rate constant ( K e) of PHT after single administration were significantly different from those in combination with CPFX. AUC and T 1/2 were decreased 160%( P < 0.01 )and 2/3 ( P < 0.05 ) separately, CL and K e were increased 144% and 133%( P < 0.01 ) respectively.