妥舒沙星对家兔体内氨茶碱药动学的研究

Effect of Tosufloxacin on Pharmacokinetics of Aminophylline in Rabbits

目的:研究妥舒沙星对家兔氨茶碱药动学的影响。方法:将18只家兔随机等分为A、B、C三组,A组经耳缘iv给予单剂量氨茶碱12．5 mg·kg-1;B、C两组家兔分别灌服妥舒沙星(每日300 mg·kg-1及450 mg·kg-1,分3次灌服),共服3 d,于第4天灌服妥舒沙星1 h后,iv与A组相同剂量的氨茶碱。结果:A、B、C三组的K分别为:0．1753,0．1341,0．1280 h-1;t1/2: 3．847,4．885,5．766 h;Vd:0．543,0．534,0．524 L;CL:0．0979,0．0759,0．0630 L·h-1;AUC:125．4,167．9,200．2μg·h·ml-1。结论:妥舒沙星使茶碱的K降低,t1/2延长,AUC增大,CL下降,对茶碱代谢的影响呈剂量依赖性。临床上妥舒沙星与氨茶碱合用时应监测茶碱的血药浓度,及时调整氨茶碱的剂量,以免引起氨茶碱中毒。

Objective： To study the effect of Tosufloxacin （TFLX） on the pharmacokinetics of Aminophylline （AMI）. Method： Eighteen healthy rabbits were divided into 3 groups （ group A ,B and C） randomly. Single dose of AMI 12.5 mg· kg^-1 was given by injection to group A, the serum concentrations of Theophylline （TP） were determined by HPLC. Group B and C were orally administered TFLX 300, 450 mg·kg^-1·d^-1 （divided 3 times） respectively for 3 days. When given AMI 12.5 mg· kg^-1 by injection after administered TFLX orally on the 4th day, the serum concentrations of TP were determined. Result： The main AMI pharmacokinetic parameters of group A,B and C were as follows：K were 0. 1753 h^-1 ,0. 1341 h^-1 and 0. 1280 h^-1 ; t1/2 were 3. 847 h,4.885 h and 5. 766 h;Vd were 0.543 L,0.534 L and 0.524L;CL were 0.0979 L·h^-1 ,0.0759 L·h^-1 and 0.0630 L·h^-1 ;AUC were 125.4 μg·h·ml^-1 ,167.9 μg· h· ml^-1 and 200.2 μg· h·ml^-1, respectivel. Conclusion： After rabbits administered TFLX, serum concentrations and A UC of TP were significantly increased ,t1/2 prolonged and CL decreased. This interaction between TFLX and AMI was dose-dependent. It was concluded that TFLX inhibits the normal metabolism of TP , interaction between TFLX and TP existed. Concentrations of the AMI must be monitored when combined with TFLX and AMI, dosage should be adjusted so as to avoid its toxicity.