Department of Pharmaceutical Science, College of Medical, Xiamen University, Xiamen 361005, China.
Phytomedicine. 2011 Apr 15;18(6):527-32. doi: 10.1016/j.phymed.2010.09.009. Epub 2010 Oct 30.
dl-Praeruptorin A (Pd-Ia), isolated from Chinese traditional herbal medicine Peucedanum praeruptorum Dunn, has been proved to be a novel Ca²+-influx blocker and K+-channel opener, and displayed bright prospects in prevention and therapy of cardiac diseases. The aim of this study was to investigate the pharmacokinetics, tissue distribution and excretion of Pd-Ia in rats following a single intravenous (i.v.) administration. The levels of Pd-Ia in plasma, tissues, bile, urine and feces were measured by a rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The results showed that Pd-Ia was rapidly distributed and then eliminated from rat plasma and manifested linear dynamics in dose range of 5-20 mg/kg. The mean elimination half-life (t(½) of Pd-Ia for 5, 10 and 20 mg/kg dose were 57.46, 60.87 and 59.01 min, respectively. The major distribution tissues of Pd-Ia in rats were spleen, heart and lung, and low polarity enabled Pd-Ia to cross the blood-brain barrier. There was no long-term accumulation of Pd-Ia in rat tissues. Total recoveries of Pd-Ia within 24 h were low (0.097% in bile, 0.120% in urine and 0.009% in feces), which might be resulted from liver first pass effect.
(dl-白花前胡甲素（Pd-Ia）是从中国传统草药白芷中分离得到的，已被证明是一种新型的 Ca²+内流阻断剂和 K+通道开放剂，在预防和治疗心脏病方面具有广阔的前景。本研究旨在研究 Pd-Ia 在大鼠体内单次静脉给药后的药代动力学、组织分布和排泄。采用快速灵敏的液相色谱-串联质谱（LC-MS/MS）法测定血浆、组织、胆汁、尿液和粪便中 Pd-Ia 的浓度。结果表明，Pd-Ia 在大鼠血浆中分布迅速，然后消除，在 5-20mg/kg 剂量范围内呈线性动力学。Pd-Ia 各剂量组的平均消除半衰期（t(½)分别为 57.46、60.87 和 59.01min。Pd-Ia 在大鼠的主要分布组织为脾、心和肺，低极性使 Pd-Ia 能够穿过血脑屏障。Pd-Ia 在大鼠组织中没有长期蓄积。24h 内 Pd-Ia 的总回收率较低（胆汁中为 0.097%，尿液中为 0.120%，粪便中为 0.009%），这可能是由于肝脏首过效应所致。
