维胺酸在大鼠体内的药代动力学  

Pharmacokinetics of N(4一carboxyphenyl)retinamide in rats

作　　者：程青[1] 顾企民 韩锐[1] 

机构地区：[1]中国医学科学院药物研究所

出　　处：《中国药理学与毒理学杂志》1994年第2期143-146,共4页Chinese Journal of Pharmacology and Toxicology

摘　　要：用高效液相色谱法测定了维胶酸（ＲⅡ）在大鼠体内的吸收，分布，排泄，生物利用度及蛋白结合率等药代动力学特性，ＲⅡ３０ｍｇ·ｋｇ－１ｉｖ，血清中药物浓度经两次加权的二室模型拟合，Ｔ１／２β为２０．７１ｈ，ＣＬｓ为０．３４Ｌ·ｋｇ－１·ｈ－１，Ｖｃ为０．９９Ｌ·ｋｇ－１．ＲⅡ１００及２００ｍｇ·ｋｇ－１ｐｏ，经一室开放模型拟合，Ｔ１／２Ｋｅ分别为１１．９２及１３．０１ｈ，ＣＬｓ为０．８７及０．７７Ｌ·ｋｇ－１·ｈ－１，体内绝对生物利用度为３９．７％及４６．４％。ＲⅡ２００ｍｇ·ｋｇ－１ｐｏ７ｈ后，肠，胃组织中ＲⅡ含量囊高，血，肝，卵巢，肾次之，心，脾，肺，睾丸，肌肉，脂肪含量较少，脑，副睾，骨组织含量极微；２４ｈ后，各组织含量明显下降，说明ＲⅡ不易在体内蓄积。１２０ｈ内主要经粪便排出，累积排出率为３４．４±ｓ２．０％，经尿液，胆汁排泄较少，累积排泄率仅分别为１．１±ｓ０．６％及０．０２４±ｓ０．０１％。经超滤法测定，ＲⅡ血药浓度在４５．９４－１０３．２２ｍｇ·Ｌ－１内，ＲⅡ血浆蛋白结合率为４６．６％一５２．４％。The absorption, distribution, excretion,bioavailability and protein binding of N一(4-carboxyphenyl) retinamide( RⅡ)in rats were reported inthe paper.Waters M244 HPLC system equipped with aM440 absorbanee deteetor(wavelength 356 nm) asusedThe analytical column was μBond-apakAM/C18 column。 Methyl alcohol一acetic acid glacia(1000 :2) were used as the mobile phase with a flow rate of 1.5mL·min-1.N-(4一ethoxycarbophenyl)retinamide(R1)was used as an internal standard The detection limit ofRⅡ was 3 ng.After iv of RⅡ 30 mg·kg-1,the dynam-ic change of he concentration of RⅡ in rat serum can becharacterized by two phases,an d the correspondinghalf-life time(T1 / 2α and T1/2β)was 0.7 and 20.71 hrespectively.The clearanee of RⅡ was 0.33 L·kg-1·h-1 and the area under the curve(AUC)was 90.3 μg·h· mL-1 Nonlinear fit of the concentration of RⅡ inthe serum following oral administration to rats atdosages of 100 and 200 mg· kg-1 demonstrated that thepeak time (Tmax )was at 4.95 and 6.23 h,the peak con-centration was 4.58 and 10.2 1 mg·L-1 in serum,theAUC was 115.06 and 260.47 mg·h·L-1 respectively,There was a traee amount of the parent drug in theserum at 48 h after the administration of RⅡ The abso-lute bioavail一ability of RⅡ was 38.2% and 43.3% byoral administration at dosages of 100 and 200 mg·kg-1.The plasma protein binding rate determined by theultra一filtration method amounted to 46.64%一52.38 %when the coneentration of RⅡ in rat plasma was in therange of 45.94 -103.22 mg·L-1.The distribution ofRⅡ in rats showed that at 7 h dosing 200 mg· kg-1 ofRⅡ(po),the highest amount of RⅡ was deteeted in thestomach and intestine and some quantity ofthe drug wasalso found in the liver,ovary and kidney.There was a lit-tle quantity of the compound in the heart,spleen,lung,muscle,testis,and a trace quantity of the compound inthe epididymis,brain,fat tissue and bone,After 24 h,on-ly very low levels of parent drug could be deteeted in theabove mentioned tissues,In the course of 120h after oral

关 键 词：维胺酸 药代动力学 高效液相色谱 

分 类 号：R979.1[医药卫生—药品]