黄芪甲苷在兔体内的药动学和在大鼠的排泄(英文)

目的 :研究黄芪甲苷在家兔体内的药动学和在大鼠的排泄。方法 :健康家兔和大鼠一次静脉注射 (静注 )给予黄芪甲苷 4mg·kg- 1,高效液相色谱 蒸发光散射检测器法检测兔血浆和大鼠尿及粪黄芪甲苷浓度 ,用 3P97药动学软件对兔血浆浓度 时间数据进行动力学分析和计算药动学参数 ,并估算大鼠体内的排泄情况。结果 :黄芪甲苷静注给药后 ,T12 α 为 0 .10h ,T12 β 为 1.4h ,Vc 为 0 .15L·kg- 1,VD 为 0 .6L·kg- 1,Cl为 0 .32L·h- 1·kg- 1,AUC为 15mg·L- 1·h。大鼠静注给药后 ,原形从尿和粪排出量分别为给药量的 16 %和 3.2 %。结论 :家兔体内黄芪甲苷的动力学过程符合二室模型 ,大鼠仅有少量原形药物从尿和粪排泄。     

氚标记的Bcl-2反义核酸(F951)在小鼠体内的药代动力学实验研究

目的　研究一种新的氚标记的Bcl 2反义寡核苷酸 3H F95 1单次静脉注射后在小鼠体内的药代动力学过程。方法　用氚标记F95 1,用液闪仪检测放射性浓度 ,用 3P87软件判断房室模型 ,计算各种参数。用液闪仪检测3H F95 1在小鼠体内各器官中的分布浓度 ,检测给药后 72h内药物从小鼠尿和粪中排泄的量。结果　3H F95 1单次静脉注射后在小鼠体内的动力学过程符合二室模型 ,3种剂量时主要的参数血浆分布半衰期 (T1/ 2α)在 10～ 15min之间 ,消除半衰期 (T1/ 2 β)在 2～ 4 5h之间。3H F95 1在肾、肝、脾、骨髓中分布浓度高于其它器官 ,在心、肺、脑、肠、皮肤、脂肪、生殖腺中也有低水平的分布。3H F95 1主要经肾从尿中排泄 ,给药后 2 4h内的累积排泄量占给药量的 5 0 47%。3H F95 1从粪中排泄的量甚微。结论　3H F95 1在小鼠体内药代动力学过程的研究为其进一步的开发具有指导价值     

[3H]洛非西定在大鼠的体内分布与排泄研究

目的 研究[3H]洛非西定在大鼠体内的分布、排泄和蛋白结合率.方法 20只大鼠灌胃[3H]洛非西定0.1 mg·kg 1后2、8、24、120 h液闪法测定组织样品和排泄物中放射性强度,用TLC法分离原型药物,用平衡透析法测定蛋白结合率.结果 药后96 h累计排泄量为95.52%,原型药物约占给药量的22.0%.灌胃后,肾、肝和心脏的药物浓度最高,血浆、脑干和脂肪的药物浓度最低.[3H]洛非西定的血浆蛋白结合率约为38%.结论 药物在体内分布广泛,且主要经粪尿排泄.     

HPLC法研究小鼠静注氢溴酸高乌甲素的药动学

目的:研究氢溴酸高乌甲素在小鼠体内的药动学。方法:小鼠单剂量静脉注射氢溴酸高乌甲素3．33 mg·kg-1,用HPLC法测定给药后不同时间的血浆药物浓度。色谱条件:Microsorb-MV 100-5 C18色谱柱(250 mm×4．6 mm,5μm),流动相为甲醇-0．1 mol·L-1磷酸二氢钠溶液(50:50),流速0．6 mL·min-1,检测波长252 nm,柱温40℃。结果:氢溴酸高乌甲素血浆浓度在0．5～15μg·mL-1范围内呈良好的线性关系,日内精密度(CV)<12％,日间CV<16％,方法回收率为69．57％～83．08％。小鼠按3．33 mg·kg-1单剂量静脉注射给药,主要药动学参数为:t1/2β= 4．726 h,总清除率(CLB)=0．318 L·kg-1·h-1,VC=0．341 L·kg-1,VB=2．167 L·kg-1,AUC0→∞=10．476μg·h·mL-1。结论:氢溴酸高乌甲素静注后在小鼠体内的药时过程符合二室开放模型,原药主要分布于周边室,消除速度适中。     

新型二膦酸盐药物药动学及组织分布的研究

目的 研究新型二膦酸盐(SC)抗骨质疏松药物在小鼠体内的分布和大鼠体内的药动学及排泄过程.方法 采用99mTc直接标记SC得到99mTe-SC,于大鼠尾静脉注射99mTc-SC后的不同时间取血,测量放射性计数,并计算药动学参数;予小鼠尾静脉注射99Tcm-SC后的不同时间处死,取主要脏器或组织,测定注射剂量率.另收集大鼠给药后不同时段的尿粪和胆汁评价排泄过程.结果 SC在体内的处置符合线性药动学,t1/2约为12 h,表观分布容积和清除率均较小,组织的分布程度低;SC在肝脏内浓聚了较多放射物质,脾脏次之,其余组织中的分布呈低水平;肾脏为SC的主要排泄器官,粪便及胆汁排泄次之.结论 研究为SC提供了药动学的基本数据.     

基因重组干扰素α-2b脂质体的药代动力学研究

研究注射用干扰素α2b脂质体在大鼠体内的药代动力学及小鼠组织分布、排泄。运用同位素示踪法结合SDSPAGE,测定静脉注射后大鼠血液中原型药物浓度并做其胆汁排泄试验;用小鼠进行组织分布试验和尿粪排泄试验。结果:符合一级消除动力学的二房室模型,干扰素α2b的t1/2β为0.69h,脂质体3个剂量的t1/2β分别为3.36h、3.02h、2.34h,干扰素α2b脂质体在大多组织中分布增加,肝脾中尤其明显。脂质体能够显著延长干扰素α2b在血液及组织中半衰期,提高靶向性。     

RP-HPLC法测普鲁托品在大鼠体内分布和排泄

目的　用反相高效液相色谱法 (RP HPLC)测定大鼠的尿、粪、肝和脑等组织中普鲁托品 (protopine ,Pro)的药物浓度 ,并对Pro在大鼠体内的分布和排泄过程进行研究。方法　流动相为甲醇、水和体积分数 2 0mol·L- 1 乙酸 (80∶2 0∶2 ) ,以ODS C1 8柱分离 ,紫外检测器检测 ,波长为 2 85nm ,生物样品在碱性条件下 ,经两次乙醚处理 ,可获得良好的分离效果。为全面了解Pro在大鼠体内的代谢过程 ,给大鼠尾静脉注射Pro 1 0mg·kg- 1 后 ,测定不同时间各组织中Pro的含量。结果　静脉给药后 ,Pro快速分布到肺、肾、脾、脑、小肠、心脏、脂肪、睾丸、肝脏、胃壁及骨骼肌、以肺、肾、脾、脑、肠组织中药物浓度较高 ,尤以肺组织浓度最高。药后 3h各组织中药物浓度下降 ,但睾丸中仍维持较高浓度。实验还发现 ,药后 5min即可测得尿中有原形药 ,1 2h尿中累积排泄量为给药量的 30 .2 1 % ,48h尿中累积排泄量为给药量的 36 87%。原形药经胆汁及粪排泄量不足 1 %。药后 5min及 1 5min血浆蛋白结合率均低于 5 %。结论　普鲁托品在大鼠体内广泛分布 ,部分经尿排泄 ,血浆蛋白结合率低     

13-甲基豆蔻酸在大鼠体内的药代动力学研究

目的　研究 1 3 -甲基豆蔻酸在大鼠体内的药代动力学。方法　用毛细管柱气相色谱法测定生物样品中的原形药物浓度 ,在大鼠体内进行血浆药代动力学、分布、排泄及血浆蛋白结合实验。结果　大鼠 ig1 3 -甲基豆蔻酸 40 0 ,80 0 ,1 2 0 0 mg· kg-1后 ,拟合的血药浓度 -时间曲线符合二室模型 ,t1/2α 为 2 .3 1 3～ 2 .843 h,t1/2β 为5 .0 99～ 6 .3 3 9h;tpeak 为 2 .2 1 5～ 2 .76 6 h;血浆蛋白结合率大于 85 .80 %。药物在大鼠体内分布广泛 ,其中心、肺、脾、肝等组织浓度较高 ,肌肉、脂肪等组织相对较低。 2 4 h粪、尿、胆汁原形药物排泄量分别为给药量的1 3 .77% ,0 .0 0 3 2 %和 0 .0 2 1 4%。结论　 1 3 -甲基豆蔻酸在大鼠体内吸收快 ,达峰时间短 ,组织分布广泛 ,血浆蛋白结合率高 ;有部分原形药物从粪便排泄     

联用丙磺舒对头孢克洛药动学的影响

目的研究与不同剂量丙磺舒(Probenecid)联用对头孢克洛(Cefaclor)药动学的影响及其定量关系,并探讨其可能机制.方法头孢克洛血、尿药浓度监测雄性家兔24只,随机分成4组.各组给药剂量如下Ⅰ组头孢克洛50 mg·kg-1;Ⅱ组头孢克洛50 mg·kg-1联用丙磺舒100 mg·kg-1;Ⅲ组头孢克洛50 mg·kg-1联用丙磺舒250 mg·kg-1;Ⅳ组头孢克洛50 mg·kg-1联用丙磺舒625 mg·kg-1.灌胃给予丙磺舒0.5 h后,再给予头孢克洛,于用药后不同时间取血、尿液样本.HPLC法测定头孢克洛血药及尿药浓度,DAS软件计算药动学参数.血浆蛋白结合率测定实验分组及剂量同上,给药1 h后取血,以平衡透析法测定头孢克洛血浆蛋白结合率.结果当丙磺舒联用剂量在0～250 mg·kg-1范围内时,随丙磺舒联用剂量增大,头孢克洛的T1/2ka、Tmax、Cmax、AUC等参数相应增大而CL/F及Vd/F相应降低(P<0.01);但当丙磺舒联用剂量达625 mg·kg-1时,头孢克洛的Cmax降低(P<0.01),AUC、CL/F则稳定于联用丙磺舒250 mg·kg-1时的水平.在本实验剂量范围内,随丙磺舒联用剂量增大,头孢克洛原型尿排泄峰时间逐渐后移,生物半衰期延长及总尿药排泄率显著降低(P<0.01).丙磺舒联用剂量在0～250 mg·kg-1范围内,随丙磺舒联用剂量增大,头孢克洛血浆蛋白结合率显著降低(P<0.01),但当丙磺舒联用剂量达625 mg·kg-1时,头孢克洛血浆蛋白结合率反与头孢克洛单用时水平相当(P>0.05).结论联用丙磺舒可以明显改变头孢克洛的药动学过程,使其Vd、CL降低,Cmax增高,AUC增大,生物半衰期延长,总尿药排泄率降低.     

注射用紫杉醇聚合物胶束在荷瘤小鼠体内的组织分布

目的:研究自制紫杉醇聚合物胶束(PTX-PM)在荷瘤小鼠体内的组织分布情况,与紫杉醇注射液(PTX-INJ)的组织分布情况比较。方法:将昆明种小鼠前肢腋皮下接种H22肝癌细胞,待瘤体长到1g。分别经尾静脉注射PTX-PM(给药剂量为50mg.kg-1)和PTX-INJ(给药剂量为20mg.kg-1)。以高效液相色谱法,于给药后不同时间测定组织中紫杉醇的药物浓度,评价2种制剂的组织分布特征和靶向性。结果:PTX-PM组明显减少血液中紫杉醇浓度,提高各组织的相对摄取率;各组织中药物浓度随剂量相应增大;紫杉醇的组织分布特征未发生改变,即肺、肝和肿瘤中分布比较多。结论:PTX-PM和PTX-INJ相比,极大降低了药物在血液中的浓度,使药物更多分布在组织中,且不改变药物对于各组织间的选择性。     

3H-去甲斑蝥素小鼠体内药代动力学与组织分布

健康小鼠灌服³H-去甲斑蝥素溶液，收集不同时间血、组织、尿和粪，采用氚标记示踪法测定放射活性，计算³H-去甲斑蝥素血浓度、单位组织放射活性及尿和粪累积排泄率，DAS软件拟合小鼠去甲斑蝥素药代动力学模型，计算其药代动力学参数，评价³H-去甲斑蝥素小鼠体内的吸收、分布及排泄过程。结果表明，小鼠灌服³H-去甲斑蝥素0.5 h后血中放射活性达峰值；15 min后小肠、胆囊、胃、肾上腺、肾脏、心脏、子宫等放射活性较高，此后逐渐降低，但3 h后胆囊、肾上腺、子宫放射活性仍较高，肾脏、肝脏等组织则较低；24 h后粪便和尿液累积排泄率分别为65.40%和1.33%。因此，小鼠口服³H-去甲斑蝥素吸收迅速，血中分布明显高于其他组织；胆囊、肾上腺、子宫分布多且持久，肝脏分布少且消除快，肾脏则分布多，但消除也快。³H-去甲斑蝥素主要经肾脏排泄，极少量经粪便排泄。由于所测放射活性为去甲斑蝥素原形及代谢物之和，应对其体内转化过程及可能代谢产物做进一步研究。     

Distribution and excretion of N-Ile1 Thr2-63-desulfatohirudin in rats

Objective To investigate distribution and excretion of N-Ile1Thr2-63-desulfatohirudin(rH)a recombinant hirudin newly developed in China,in rats for its development as a novel anticoagulant agent.Methods ELISA was used to determine the rH concentration in related tissues and body fluids.Tissues were collected at 15,60 and 180min respectively,after iv administration of rH 1.0 mg·kg-1 to 3 groups of 5 rats,and homogenized.Urine,bile and feces were collected at pre-selected intervals of time after iv dosing 1.0 mg·kg-1 to 3 groups of 5 rats and assayed.Results rH following iv dosing was distributed rapidly,the rH levels in all tissues being found to be the highest at 15 min post-injection,afterwards gradually reduced.The highest concentration of rH was found in blood,the next in lung and heart,the lowest in brain.With 15 min post dose as an example,the rH contents in tissues were ranked in order of plasma>lung>heart >adipose>skeletal muscles>kidney>liver>spleen>brain.The 12 h-cumulative excretion amount of rH in urine and feces accounted for 0.03%and 0.001% of administered dose,respectively;the 6 h-cumulative excretion amount in bile was 0.02%of the dose.Conclusions The rH is distributed mainly in blood circulation system with very low content in other tissues.The drug is excreted from urine,feces and bile of rats in extremely minute amount(only 0.051% dose),suggesting that rH undergoes extensive metabolic elimination in rat body.     

Canrenoate disposition in dogs

Summary The metabolism and tissue distribution of intravenously administered C¹⁴-canrenoate-potassium (CR-K) was studied at various time intervals in 10 dogs. After a rapid decline of total radioactivity immediately after injection, the elimination in plasma occurred in two distinct phases with half-lives of 6.8 and 23.6 h. Canrenoate was rapidly converted to lipid- and water-soluble metabolites which were separated by thinlayer chromatography. Most tissues showed similar concentrations of total radioactivity as plasma. An accumulation of radioactivity per g wet weight was detected in the adrenal glands and fat tissue as well as in the metabolic and excretory organs but not in the heart. Taking into consideration that skeletal muscle, fat tissue and liver constitute about 64% of the body weight, it is obvious that the main part of total radioactivity was present in these tissues. In contrast to plasma, urine and feces, where various metabolites could be analysed, the bulk of radioactivity in tissues is represented by canrenone. Thus, the estimation of the parent compound and its metabolites in plasma, urine and feces does not allow final conclusions about the active substance in various tissues. Within 72 h 47% of the dose was recovered in urine and 49% in feces.     

Elimination pathways of [14C]losoxantrone in four cancer patients.

Losoxantrone is an anthrapyrazole derivative in Phase III development in the U.S. for solid tumors, notably breast cancer. To obtain information on the routes of elimination of the drug, a study was conducted in four patients with advanced solid tumors, which involved intravenous administration of 100 microCi of [14C]losoxantrone for a total dose of 50 mg/m(2) during the first course of losoxantrone therapy. Blood, urine, and feces were collected for up to 2 weeks and were analyzed for total radioactivity and parent drug. In addition, feces were profiled for the presence of metabolites. Plasma concentrations of total radioactivity exhibited a temporal pattern similar to the parent drug. Combined recovery of administered total radioactivity from urine and feces was 70% with the majority (87%) of this radioactivity excreted in the feces, presumably via biliary excretion. Feces extracts were profiled for metabolites using a high-performance liquid chromatography method developed to separate synthetic standards of previously identified human urinary metabolites. Only intact losoxantrone was found in the feces. About 9% of the dose was excreted in the urine, primarily during the first 24 h and mostly in the form of parent compound. Collectively, these data indicate that fecal excretion of unmetabolized drug via biliary and/or intestinal excretion is the primary pathway of intravenously administered losoxantrone elimination in cancer patients with refractory solid tumors.     

Disposition of 2-(2-quinolyl)-1,3-indandione (D. C. yellow #11) in rats dosed orally or intravenously

The disposition of 2-(2-quinolyl)-1,3-indandione (D. C. yellow #11, DCY) in male Fischer rats dosed intravenously or by feeding was determined. For rats given [14C]DCY in the feed (0.00044-0.41% of the diet), recovery of radioactivity during the 24-h dosing period and the 72-h period thereafter ranged from 89.1 to 93.9% for feces and from 4.98 to 6.25 for urine. Tissues contained only trace amounts. Following intravenous dosing with [14C]DCY (0.93 mg/kg), radioactivity distributed readily into most tissues; maximum amounts were present at 5 min, the earliest time of assay. Maximum amounts of radioactivity in fat, skin, and gut tissue, however, were present at 30 min after dosing. These three tissues also had relatively long alpha phases for the elimination of radioactivity. In 24 h after intravenous dosing, rats excreted 81.1% of the dose in the feces and 16.0% of the dose in the urine. For rats fitted with biliary cannulas, 54.5% of the dose, all of which was metabolites of [14C]DCY, was recovered in the bile in 4 h. Associated with the rapid and extensive biliary excretion of metabolites of intravenously administered [14C]DCY was the appearance of large amounts of radioactivity in the feces and also, at intermediate time points, in the liver, gut contents, and gut tissue. In conclusion, rats rapidly distribute, metabolize, and excrete [14C]DCY.     

口服抗肿瘤药赛特铂在大鼠的药动学

目的 :观察口服抗肿瘤药赛特铂(satraplatin)在大鼠的药动学。方法 :石墨炉原子吸收分光法测定体内赛特铂的总铂浓度。结果 :剂量为 5 0mg·kg- 1和 10 0mg·kg- 1时 ,主要药动学参数分别为 :T12 β(4 3±s 34)h和 (5 8± 38)h ,Tmax(5 .0± 2 .0 )h和 (6 .0± 1.0 )h ,Cmax(12 .6± 2 .5 )mg·L- 1和 (13.4± 1.5 )mg·L- 1,AUC0 ∞(4 2 2± 12 0 )mg·h·L- 1和 (70 2± 118)mg·h·L- 1。组织分布以肝、肾最高。 4 8h后药物排出已基本完成 ,主要经粪便排出 ,约 5 5 % ,尿排出小于 6 % ,2 4h胆中排出0 .2 3%。结论 :赛特铂的药时曲线为口服一级吸收2室模型。     

R—hap在大鼠体内的组织分布，排泄及药动学研究

测定R-hap在健康Wistar大鼠体内的组织分布，排泄及药动学参数。R-hap采用IODO-GEN标记，测定单次推注给药后^125I-R-hap的组织分布，尿、粪及胆汁的排泄情况。^125I-R-hap药动学参数也是在单次推注给药后测定。R-hap在体内广泛分布，在大部分器官中快速消除。其中肾的含量最高，脂肪的含量最低。累计排泄率为71．81％±2．15％（48小时）及94．71％±1．50％（120小时）。经尿排泄为主要的排泄途径，给药后120小时，尿及粪的累计排泄率分别为80．64％±1．47％，14．07％±0．95％。平均给药时曲线下面积为（8818．4±576．1）Bq／h／mL。R-hap的组织分布，排泄及药动学参数的结果为未来的临床试验设计提供了参考依据。     

Metabolism, excretion, and pharmacokinetics of [14C]tigecycline, a first-in-class glycylcycline antibiotic, after intravenous infusion to healthy male subjects.

Tigecycline, a novel, first-in-class glycylcycline antibiotic, has been approved for the treatment of complicated intra-abdominal infections and complicated skin and skin structure infections. The pharmacokinetics, metabolism, and excretion of [(14)C]tigecycline were examined in healthy male volunteers. Tigecycline has been shown to bind to bone; thus, to minimize the amount of radioactivity binding to bone and to maximize the recovery of radioactivity, tigecycline was administered intravenously (30-min infusion) as a single 100-mg dose, followed by six 50-mg doses, every 12 h, with the last dose being [(14)C]tigecycline (50 microCi). After the final dose, the pharmacokinetics of tigecycline in serum showed a long half-life (55.8 h) and a large volume of distribution (21.0 l/kg), whereas radioactivity in serum had a shorter half-life (6.9 h) and a smaller volume of distribution (3.3 l/kg). The major route of elimination was feces, containing 59% of the radioactive dose, whereas urine contained 32%. Unchanged tigecycline was the predominant drug-related compound in serum, urine, and feces. The major metabolic pathways identified were glucuronidation of tigecycline and amide hydrolysis followed by N-acetylation to form N-acetyl-9-aminominocycline. The glucuronide metabolites accounted for 5 to 20% of serum radioactivity, and approximately 9% of the dose was excreted as glucuronide conjugates within 48 h. Concentrations of N-acetyl-9-aminominocycline were approximately 6.5% and 11% of the tigecycline concentrations in serum and urine, respectively. Excretion of unchanged tigecycline into feces was the primary route of elimination, and the secondary elimination pathways were renal excretion of unchanged drug and metabolism to glucuronide conjugates and N-acetyl-9-aminominocycline.     

Absorption,Metabolism, and Excretion of 2,3:4,5-Bis(2-Butylene) Tetrahydro-2 Furaldehyde (Mgk R11)in the Rat

Abstract

Experiments were conducted in four groups of rats to determine the absorption, distribution, metabolism, and excretion (ADME) patterns following oral administration of [formyl-¹⁴C] 2,3:4,5-bis(2-butylene) tetrahydro-2 furaldehyde (MGK R11).

Ten rats (five males and five females) were used in each of the four experiments. Fasted rats were administered [for-myl-¹⁴C] MGK R11 at a single oral dosage of 65 mg/kg, at a single oral dosage of 1000 mg/kg, and at a daily oral dosage of 65 mg/kg of nonradiolabeled compound for 14 days followed by a single dose of ¹⁴C-labeled compound at 65 mg/kg. Rat blood kinetics were determined in the fourth group following a single oral dose of 65 mg/ kg. Each animal was administered approximately 12–14 μCi of radioactivity.

Urine and feces were collected from all groups at predetermined time intervals. Seven days after dose administration, the rats were euthanized and selected tissues and organs were harvested. Samples of urine, feces, and tissues were subsequently analyzed for ¹⁴C content.

In the blood kinetics study, radioactivity peaked at approximately 30 min in both the males and females, indicating very rapid absorption. The decline of radioactivity from blood followed a biphasic elimination pattern. The first half-life was 1.36 h for males and 1.18 h for females. In the second phase, the half-life was 21 h for males and 26 h for females.

Female rats excreted 67.21-86.85% of the radioactivity in urine and 13.99–28.08% in feces, whereas male rats excreted 50.19–64.37% of the administered radioactivity in urine and 31.43–40.94% in feces. Tissue residues of ¹⁴C ranged between 0.47% and 1.09% of the administered dose. The total mean recovered radioactivity of the administered dose in the four definitive studies ranged between 92% and 101%. No parent compound was detected in the urine.

Three major and one minor metabolite was isolated by high-performance liquid chromatography (HPLC) and identified by gas chromatography/mass spectrometry (GC/MS). One major metabolite was formed by oxidation of the aldehyde moiety to the carboxylic acid. A second metabolite was the glucuronic acid conjugate of the carboxylic acid and the third was formed by reduction of the aldehyde moiety of MGK R11 to an alcohol followed by glucuronic acid conjugation. The minor metabolite was the unconjugated alcohol derivative of MGK R11.

The gender of the animals affected the rate, route of excretion, and metabolic profile. The urinary excretion rate was faster in females than in males and the amount excreted was also greater in female rats.