隐丹参酮的吸收、分布、排泄和代谢

本文应用薄层层离法及双波长薄层色谱扫描仪分离及测定了生物样品中隐丹参酮的含量,并用此法研究了隐丹参酮在动物体内的吸收、分布和排泄过程。药物自胃肠道吸收后,大部分在体内转化。大鼠口服隐丹参酮后,胆汁中代谢产物随给药时间的延长逐渐增多。共得7个代谢产物。有隐丹参酮,丹参酮Ⅱ-A,丹参酮Ⅱ-A的羟基化产物及丹参酮Ⅱ-A与谷氨酸的缩合物等。有4个代谢产物有抑菌活性,但以原形药作用最强,后者可能是在动物体内发挥抗菌作用的主要形式。

ABSORPTION, DISTRIBUTION, EXCRETION AND METABOLISM OF CRYPTOTANSHINONE

A method using thin layer chromatography and dual wavelength. TLC scanner for isolation and quantitative determinination of cryptotanshinone in biological specimens was described. After oral administration of cryptotanshinone to mice, the half life of the drug in the gastrointestinal tract was found to be 3 1/3 hrs. High drug levels were found in the liver, lung, brain and heart 2 hrs after oral administration of cryptotanshinone. The drug levels in the spleen, plasma and kidney were very low. After intravenous injection, the highest drug level was found to be in the brain. In rats only 0.34% of the dose was recovered in the 48-hr urine as unchanged drug after a single oral dose. It is likely that a great part of the drug was metabolized in the body.In rats given an oral dose of cryptotanshinone, seven metabolites were isolated from urine and bile and identified. It was shown that metabolite NO. 6 was unchanged drug, NO. 7 was tanshinone Ⅱ-A, NO. 4 and NO. 5 were hydroxyl forms of tanshinone Ⅱ-A, while NO. 1 was considered to be a glutamic acid conjugate of tanshinone Ⅱ-A. NO. 2, 3, 5 and 6 were shown to have bacteriostatic activity against Staphylococcus aureus (in vitro). The antimicrobial action of NO.6 (unchanged drug) was much stronger than that of the others. Therefore, the unchanged drug was probably the main pharmacologically active form in the body.