雷公藤内酯酮在大鼠体内的药代动力学和体内处置研究  

PHARMACOKINETICS AND DISPOSITION OF TRIPTONIDE IN RATS

作　　者：岗艳云[1] 张正行 张胜强 刘晓东 安登魁 

机构地区：[1]中国药科大学中昆药剂研究所

出　　处：《药学学报》1996年第12期901-905,共5页Acta Pharmaceutica Sinica

摘　　要：采用ＲＰ－ＨＰＬＣ法，测定给药后不同时刻大鼠血浆中雷公藤内酯酮的浓度。大鼠ｉｖ０．７，１．４，２．８ｍｇ·ｋ－１雷公藤内酯酮后，血浓数据用ＰＫＢＰ－ＮＩ程序拟合，药物动力学模型为两室开放模型，Ｔ１／２α为０．１６７～０．１９５ｈ，Ｔ１／２β为４．９５～６．４９ｈ，曲线下面积（ＡＵＣ）与剂量成正比，清除率（ＣＬｓ）与剂量无关。非房室模型统计矩计算的结果表明，３剂量平均驻留时间ＭＲＴ为３．２６～５．１４ｈ。大鼠ｉｖ雷公藤内酯酮后，在大鼠体内分布广泛，其中以肺和肝药物浓度最高，心、肾、脾和肌肉次之，宰丸、胃肠道和脑中最低。ｉｖ雷公藤内酯酮后，经尿和胆汁排泄的原型药物较少。雷公藤内酯酮的血浆蛋白结合率约为７５％。Triptonide,isolated from Tripterygium wilfordii Hcok.,was found to showsignificant antiinflammatory,immunosuppression and antitumor activities.A RP-HPLC methOd wasapplied to determine the plasma concentration of triptonide at different times in rats.Concentration-time curves after iv 0.7,1.4 and 2.8 mg·kg-1 of triptonide were fitted to a two-compartment openmedel with T1/2αof 0.167～0.195 h and T1/2βof 4.95～6.49 h.The area under curves(AUCs)were linearly related to the dosages(r=0.9894).Systematic clearances(CLs) were independent ofdOsages.Mean residence time(MRT) of the three doses was 3.26～5. 14 h by noncompartmental(the statistical moment methed)analyses,The tissue distribution of triptonide in rats appeared to bewide throughout the body.The triptonide levels were high in the lung and liver,mederate in theheart,kidney,spleen and muscle and low in the testis,intestine and brain. Data of the urine and bileexcretion indicated that only a small percent of unchanged triptonide was excreted.Plasma proteinbinding of triptonide rate was about 75%.

关 键 词：雷公藤内酯酮 药代动力学 组织分布 

分 类 号：R969.1[医药卫生—药理学]