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目的 :研究口服马兜铃酸I(AA I)在大鼠体内的药物代谢动力学特点。方法 :以12 5I标记的AA I作为示踪剂 ,给予大鼠一次口服关木通水煎剂 10g·kg-1和12 5I标记AA I(含AA I37.2mg·L-1)的混合药液 ,测定全血12 5I AA I浓度及血浆蛋白结合率 ,采用 3P87程序拟合并计算药物代谢动力学参数。同时测定肝、肾等 9种脏器中的12 5I AA I含量 ,计算ID %、分布比值 ,观察上述指标随时间的动态变化 ,分析比较AA I在不同脏器的分布特点。结果 :大鼠一次口服关木通水煎剂后 ,AA I迅速吸收入血 ,于 30min达到高峰 ,持续至 1.5h ,随后其浓度逐渐降低 ,于 2 4h后仅存微量 ,给药后 10d时 6 8.9%的AA I以蛋白结合形式存在。经拟合其特征符合血管外给药二室模型 ,所得参数显示 :口服AA I在 0 .74h达峰 (Tmax) ,达峰浓度 (Cmax) 0 .92mg·L-1,分布半衰期 (t1/ 2α) 0 .6 8h ,消除半衰期 (t1/ 2 β) 2 0 .4 6h ,表观分布容积 (V/F) 87.39mL ,总清除率CL(s) 5 .85mL·h-1(0 .10mL·min-1)。服药后AA I迅速分布至全身 ,5min时即已达到分布比值的高峰 ,2 4～ 4 8h处于最低水平 ;而后AA I在肝、肾的分布比值又不断增高 ,肝脏在第 4d达峰 ,而后再次下降 ;在肾脏则继续升高 ,至观察结束 (第 4 0d)最为突出 ,明显高于其他脏器 (P <0 .
Objective: To study the pharmacokinetics of oral aristolochic acid I (AA I) in rats. METHODS: The rats were given one oral Aqueous Aqueous Extract (10g·kg-1) and 12 5I AA I (containing AA I37.2mg·L-1) as the tracer. The concentration of 125I AA I in whole blood and plasma protein binding were measured. The 3P87 program was used to fit and calculate the pharmacokinetic parameters. Simultaneous determination of 12 5I AA I content in 9 organs such as liver and kidney, calculation of ID%, distribution ratio, observation of the dynamic changes of the above indicators over time, analysis and comparison of AA I distribution in different organs. RESULTS: After oral administration of Guan Mu Tong decoction, the rats quickly absorbed AA I into the blood and reached a peak at 30 min, continued until 1.5 h, and then gradually decreased its concentration. After 24 h, only trace amounts were observed, and after 6 d, 68.9 % of AA I exists in protein bound form. Fitted by its characteristics in line with the extravascular delivery of the two-compartment model, the obtained parameters showed that the oral AA I peaked at 0.74h (Tmax), reached the peak concentration (Cmax) 0.92mg·L-1, and the distribution half-life (t1/ 2α) 0 . 6 8h, elimination half-life (t1/ 2 β) 2 0 . 4 6h, apparent volume of distribution (V/F) 87.39mL, total clearance CL(s) 5.85mL·h-1 (0. 10 mL·min-1). After taking the drug, AA I rapidly distributed to the whole body, reached the peak of distribution ratio at 5 minutes, and was at the lowest level from 24 to 48 hours; then the distribution ratio of AA I in the liver and kidney increased continuously, and the liver peaked at the 4th day. It decreased again; in the kidney it continued to rise until the end of the observation (40th day) was the most prominent, significantly higher than other organs (P <0.