蒿苯酯在大鼠的药物代谢动力学

PHAKMACOKINETICS OF ARTENIBENZOATE IN RATS

大鼠ｉｇ蒿苯酯后吸收迅速，其药时曲线出现双峰现象。ＳＰＬＩ非房室模型统计矩计算结果表明，３剂量组平均驻留时间ＭＲＴ约在１２ｈ，半衰期Ｔ１／２约在８ｈ，基本一致。将前８ｈ第一峰血药浓度曲线用３Ｐ８７程序拟合，药代动力学模型为一室模型。大鼠ｉｇ蒿苯酯后２ｈ药物可广泛分布于各组织，６ｈ后各组织中药物浓度均很低。ｉｇ蒿苯酯后主要经尿排出，４８ｈ经粪尿累积排出７０．４％。蒿苯酯平均血浆蛋白结合率约为７０％。提取物形式的鉴别结果表明，大鼠ｉｇ蒿苯酯后血中以蒿苯酯原型药为主，尿中蒿苯酯及还原青蒿素均有，粪中则以还原青蒿素为主。

Artenibenzoate is a new schistosomacide.This paper reports the pharmacokineticsof artenibenzoate in rats after oral administration.The concentrations in biological samples weredetected by spectrophotometry.The concentration time curve of the drug in plasma showed a double-peak after 150,300 and 600 mg·kg-1 ig.Artenibenzoate absorption was fast and peak plasma levelwas found 1h after administration.Then,the drug level declined to the lowest in 8 h.A secondabsorption peak appcared in 12 h.Two hours after oral administration to normal rats,the highest levelof artenibenzoate was present in the stomach wall,while appreciable level was found in testicle,liver,spleen,heart,kidney and lung.Artenibenzoate in fat and intestine was lower,almost no drug wasdetected in brain and muscle.Six hours after oral administration,the drug concentration in varioustissues decreased rapidly,but that in testicle,heart,kidney and fat decreased slowly.Urinaryexcretion was an important route of excretion.Artenibenzoate excreted in urine was about 45.6%ofthe administered dosage and that in feces 24.8%within a 48 hours period.The excreted amount inbile was 0.54%within 36 hours.Plasma protein binding of artenibenzoate was about 70%.Majorunchanged artenibenzoate was detected in the extract from plasma,major reduced-arteannuin fromfeces,and both unchanged artenibenzoate and reduced -arteannuin from urine after oral administrationin ratsa.