非洛地平对兔体内茶碱药动学的影响

Effect of Felodipine on Pharmacokinetics of Theophylline in Rabbits

目的 :观察新西兰白兔灌服非洛地平前后茶碱血药浓度及药动学参数的改变。方法 :实验分为两期 ,Ⅰ期 :6只兔单独灌服氨茶碱 ,连续给药 4d后定时采血 ;Ⅱ期 :合用非洛地平与氨茶碱 7d ,每次给药量氨茶碱 3 0mg·kg 1 ,非洛地平 1mg·kg 1 。采用荧光偏振免疫分析法测定茶碱血药浓度。对两期药动学参数进行统计分析。结果 :与Ⅰ期比较 ,Ⅱ期的消除半衰期 (t1 2 β)、消除速率常数 (Ke)、表观分布容积 (V·C F)差异有极显著性或差异有显著性 (P <0 .0 1,P <0 .0 5 ) ,AUC、Cmax、tmax、Ka、t1 2α均差异无显著性 (P >0 .0 5 )。结论 :长期合用非洛地平和氨茶碱 ,非洛地平能延缓茶碱在兔体内的消除 ,但需要密切监测茶碱的血药浓度。

Objective:To investigate the effect of oral felodipine on serum concentrations and its pharmacokinetics of theophylline in New Zealand rabbits. Method:The serum concentration of theophylline was determined by FPIA in rabbits having taken aminophylline or aminophylline combined with felodipine. The experiment was divided into 2 stages. The subjects only received a 4 day course of oral aminophylline (Ⅰ), aminophylline and felodipine were coadministrated for 7 day (Ⅱ). The dose of aminophylline was 30 mg·kg -1 and the dose of felodipine was 1 mg·kg -1 for rabbits. The two series of pharmacokinetics parameters were analysed by statistic method. Results:Compared to stage Ⅰ, t _ 1/2β ? Ke ? V · C/F changed markedly at stage Ⅱ ( P <0.05, P <0.01), and there was no significant variation in modification of other pharmacokinetics parameters. Conclusion:Felodipine may delay the elimination of theophylline when they are used in combination for a long time in rabbits. It is suggested that the blood concentration of theophylline must be monitored when the drug is taken with felodipine.