尼群地平对兔体内茶碱的药动学影响

Effect of nitrendipine on pharmacokinetics of aminophyllin in rabbit

目的 :研究氨茶碱与尼群地平合用时是否需调整其剂量。方法 :建立以 β 羟基茶碱为内标而检测血清茶碱的高效液相色谱法 ,8只大白兔于第 1、7天单次静注氨茶碱 12 .5mg·kg-1,第 2～ 7天灌服尼群地平 10mg·kg-1,bid。用氨茶碱后各时间点静脉采血 ,测定茶碱血药浓度 ,用 3P87药动学软件计算参数 ,用t检验进行统计。结果 :单用氨茶碱与合用尼群地平的药时曲线呈二室开放模型 ,T1/2α分别为 (1.9± 0 .7) ,(1.4± 0 .8)h ;T1/2 β分别为 (14.4± 8.3) ,(17.8± 2 0 .0 )h ;MRT分别为 (6 .4±1.0 ) ,(6 .2± 0 .6 )h ;Cl分别为 (6 8.1± 15 .6 )× 10 -3 ,(77.9± 16 .6 )× 10 -3 L·kg-1·h-1;AUC分别为 (16 1.8± 2 2 .2 ) ,(15 2 .5± 35 .1)mg·L-1·h。结论 :所有药动学参数经t检验 ,P >0 .0 5 ,说明尼群地平对茶碱的药动学无影响。

OBJECTIVE:To study the dose adjustment of aminophylline when used in combination with nitrendipine.METHODS:A senstive specific and rapid HLPC method for the determination of theophylline in serum was developed with β-hdydroxyethyltheophylline as internal standard.A single intravenous dosage of 12.5mg·kg -1 aminophylline on 1st and 7th day,twice oraly of dosage 10mg·kg -1 nitrendipine from 2 to7 day have been taken in 8 rabbits.Theophylline in the serun was determined after aminophylline have been taken.The data were analysed with the progame of 3P87 to get pharmacokinetics.RESULTS:The concentrantion-time cures of theophylline which both the single and combination theophylline fitted two-compartement kinetic mode.The main parmeters were as follows: T 1/2α was ( 1.9 ± 0.7 ),( 1.4 ± 0.8 )h; T 1/2β was ( 14.4 ± 8.3 ),( 17.8 ± 20.0 )h, MRT was ( 6.4 ± 1.0 ),( 6.2 ± 0.6 )h, Cl was ( 68.1 ± 15.6 )×10 -3 ,( 77.9 ± 16.6 )×10 -3 L·kg -1 ·h -1 ; AUC was ( 161.6 ± 22.2 ),( 152.5 ± 35.1 )mg·L -1 ·h, reslpectively.CONCLUSIONS:All prarmeters between sigle dosage and combination had no significant difference ( P > 0.05 ).No effect of nitrendipine on pharmacokinetics of aminophylline in rabbit.