3H-紫草素的吸收、组织分布和排泄

本文研究了³H标记的紫草素(shikonin)在小鼠体内的代谢。静脉注射³H紫草素后,血浆消除相半衰期(T 1/2β)为8.79 h,分布容积(V_d)为8.91 L/kg。静脉注射后胆汁及肝中含量最高,肺、脾、肾、心、皮肤中等,睾丸,肌肉、脑含量最低。肌肉注射及灌胃后吸收迅速,血浆浓度达峰时间分别为7.62min和5.78 min。静脉注射后,仅有小部分以原形药从屎及粪排出,大部分以转化形式排出。

A STUDY ON ABSORPTION, DISTRIBUTION AND EXCRETION OF 3H-SHIKONIN IN MICE

Shikonin is one of the active components isolated from the root of Arnebia euchrona (Royle) Johnst. Shikonin has been shown to possess significant anti-inflammatory and anti-tumor activities and has been used clinically in phlebitis and vascular purpura with fairly good results. In the present work, the absorption, distribution and excretion of shikonin was studied in mice using tritium labeled compound.The plasma concentration-time curve obtained after intravenous injection of ³H-shikonin (77 μCi/kg) to mice was shown to fit a three compartments open model with the following pharmacokinetic parameters:P=693690 dpm/ml A=110563 dpm/ml B=11750 dpm/mlp=42.3/h α=1. 29/h β=0.0727/hT1/2p= 0.0151h T1/2α=0.496h T1/2β=8.79hK12=29.2/h K21=7.36/h K13=3.81/hK31=0.174/h Kel=3.09/hAUC=263770 dpm/L.h Vc=2.09 L/kgVd=8.9 L/kg CL=0.646 L/kg/hThe drug concentration was found to be high in bile anti liver, moderate in lung, spleen, kidney, heart and skin and low in testis, muscle and brain.The absorption of ³H-shikonin (77 μCi/kg) was rapid after oral or intramuscular administration. In both cases, radioactivity could be detected from the plasma about 1 min after administration and reached peak levels at 5.78 min and 7.62 min, respectively. The bioavailability was 34.3% for the former route and 64.7% for the latter.Within 96 h following ⅳ injection, the total radioactivity excreted in urine and feces was 40.5% and 40.3% of dose, respectively, of which only 3.6% and 7.7% were unchanged drug.