~3H-氧化苦参碱在小鼠及大鼠体内的代谢

The Metabolism of ~3H-oxymatrine in Mice and Rats

用同位素示踪及整体放射自显影法研究~3H-氧化苦参碱在小鼠及大鼠体内的代谢。静脉注射的血药浓度-时间曲线符合二室开放模型。T 1/2α=4.9min,T 1/2β=2.1h。肌肉注射时胆囊,肾、肝、肠中放射性最高。药物主要经尿排泄,给药后48h内排出给药量的82.6％,而粪便中排出仅占给药量的6.4％。尿中除原型药外还有苦参碱。胆汁也是重要的排泄途径,但大部分又在肠中重吸收。生物转化部位是在胃肠道和肝。

In this paper, the absorption, distribution and elimination of 3H-oxymatr-ine in mice and rats are reported. After intravenous injection of 3H-oxyma-trine the shape of the blood radioactivity level versus time curve was fitted to a two-compartment open model with T1/2α = 4, 9 min and T1/2β = 2. 1 h. After intramuscular injection to mice, the highest level of radioactivity was found in the gall-bladder, kidney, liver and intestine. Next comes the heart, lung, spleen, stomach, thymus, bone marrow, skin-hair and muscle. The radioactivity levels in the brain, testis, bone and fat were low. These results indicate that 3H-oxymatrine is distributed widely in the body and eliminated rapidly. The total urinary excretion of radioactivity in mice was found to be about 82.6% within 48 h, while about only 6.4% was present in the feces. Not only unchanged oxymatrine was excreted from the urine but also a metabolite matrine. Biliary excretion was an important route of elimination. Rats excreted 28.3% of the administered radioactivity from the bile within 8 h. However the radioactivity was mostly absorped from the intestine due to entero-hepatic circulation. Oxymatrine was found to be partly biotransformed to matrine in the gastrointestinal tract and liver.