三尖杉酯碱脂质体在兔体内的药物动力学

本文比较了游离三尖杉酯碱(free harringtonine,FH)和其高、低包裹率脂质体(high and low en-capsulation percentage harringtonine liposmes,En％HL)在兔体内的药物动力学行为,ⅳ FH,low En％HL和high En％HL的药时曲线均符合双室开放模型,FH,low En％HL和high En％HL的α,β两相的生物半衰期分别为:1.32±0.24,32±6 min;4.12±0.25,106±5 min;9.4±1.2,209±5 min。     

三尖杉酯碱脂质体在兔体内的药物动力学

本比较了游离三尖杉酯碱和其高，低包裹率脂质体在兔体内的药物动力学行为。ｉｖＦＨ，ｌｏｗＥｎ％ＨＬ和ｈｉｇｈＥｎ％ＨＬ和ｈｉｇｈＥｎ％ＨＬ的α，β两相的生物半衰期分别为：１。３２±０。２４，３２±６ｍｉｎ；４．１２±０。２５，１０６±５ｍｉｎ；９．４±１。２，２０９±５ｍｉｎ．     

马钱子生物碱在大鼠体内的药代动力学研究马钱子生物碱在大鼠体内的药代动力学研究

目的用反相高效液相色谱法研究马钱子砂烫炮制品中生物碱在大鼠体内的药代动力学。方法HPLC法,色谱柱为Hypersil BDS C₁₈,流动相为乙腈-水,流速0.8 mL·min^-1,检测波长254 nm。结果大鼠iv本品后,其主要成分士的宁、马钱子碱、士的宁氮氧化物和马钱子碱氮氧化物的代谢均符合二室开放模型,主要药代动力学参数分别如下:T_1/2α为(8±5), (4±3), (6.2±1.7) 和(3.0±0.8) min,T_1/2β为(262±125), (416±131), (285±50)和(342±141) min,CL为(17±4), (21±12), (1.9±1.8)和(2.8±1.1) mL·min^-1,V_c为(1.4±0.5), (1.7±1.1), (0.24±0.16)和(0.23±0.06) L·kg^-1,V_d为(6.0±1.2), (12±7), (0.8±0.6)和(1.5±0.6) L·kg^-1,AUC为(57 578±25 578),(35 240±15 616),(93 088±22 375)和(177 712±120 110) h·μg·L^-1。结论此法为人体内的药代动力学研究提供参考。     

马钱子生物碱在大鼠体内的药代动力学研究

目的用反相高效液相色谱法研究马钱子砂烫炮制品中生物碱在大鼠体内的药代动力学.方法 HPLC法,色谱柱为Hypersil BDS C18,流动相为乙腈-水,流速0.8 mL*min-1,检测波长254 nm.结果大鼠iv本品后,其主要成分士的宁、马钱子碱、士的宁氮氧化物和马钱子碱氮氧化物的代谢均符合二室开放模型,主要药代动力学参数分别如下:T1/2α为(8±5), (4±3), (6.2±1.7) 和(3.0±0.8) min,T1/2β为(262±125), (416±131), (285±50)和(342±141) min,CL为(17±4), (21±12), (1.9±1.8)和(2.8±1.1) mL*min-1,Vc为(1.4±0.5), (1.7±1.1), (0.24±0.16)和(0.23±0.06) L*kg-1,Vd为(6.0±1.2), (12±7), (0.8±0.6)和(1.5±0.6) L*kg-1,AUC为(57 578±25 578),(35 240±15 616),(93 088±22 375)和(177 712±120 110) h*μg*L-1.结论此法为人体内的药代动力学研究提供参考.     

辣椒碱多囊脂质体的制备及在大鼠体内的药动学研究

目的 制备辣椒碱多囊脂质体,并考察其包封率和在大鼠体内的药动学.方法采用复乳法制备辣椒碱多囊脂质体、单因素筛选处方,并考察大鼠sc辣椒碱多囊脂质体后的体内药动学.结果制备的辣椒碱多囊脂质体的外观圆整,大小均匀,包封率为71.9%±3.8%,平均粒径为8.1 μm.大鼠sc辣椒碱多囊脂质体后,与辣椒碱溶液相比,Cmax分...     

莲心碱在大鼠体内的药物动力学研究

用反向HPLC法 ,以己酮可可碱为内标 ,建立了血浆中莲心碱的测定方法 ,血浆标准曲线为A1/A2 =0 3188C - 0 0 6 77,相关系数r =0 9999,回收率及日内、日间精密度均符合要求。根据大鼠颈静脉给药 (8 5 4mg/kg)后测得的血药浓度 ,用 3P87处理后求得的莲心碱的主要药动学参数为 :t1/ 2 (α) =2 5 14min ,t1/ 2 ( β) =49 5 2 2min ,AUC =114 878min·μg/mL ,CL =0 0 743L/ (kg·min) -1,V(c) =0 76 6L/kg。     

血根碱脂质体的制备与大鼠体内药动学

目的：制备血根碱脂质体并研究其在大鼠体内的药动学。方法：采用硫酸铵梯度法制备血根碱脂质体。大鼠尾静脉注射血根碱脂质体或血根碱溶液,血浆样品用甲醇沉淀蛋白提取,以白屈菜红碱为内标,HPLC法测定。应用Kinetica4．4拟合数据,求算药动学参数。色谱条件如下：采用色谱柱Zorbax SB—C18（250mm×4．6mm,5μm）,流动相为乙腈～0．1％磷酸水溶液（30：70）,流速1mL·min^-1,荧光检测激发波长475nm,发射波长为577nm。结果：溶液组和脂质体组的t1/2,β分别为62．44min、73．65min,AUC分别为120．5mg·min·L^-1、182．2mg·min·L^-1,经t检验两组有显著差异。结论：上述方法能够准确、灵敏地检测血浆中的血根碱。血根碱制备成脂质体后在大鼠体内消除变慢．生物利用度增加。     

高效液相色谱法同时测定马钱子总生物碱脂质体中士的宁和马钱子碱的含量

目的:采用高效液相色谱法测定马钱予总生物碱脂质体中马钱子碱和士的宁的含量.方法:马钱子总生物碱脂质体与甲醇按1:9混合后离心取上清液用甲醇稀释进样.色谱条件:采用Lichrospher C18柱(4.6 mm×250 mm,5μm),乙腈-0.01mol·L-1庚烷磺酸钠与0.02 mol·L-1磷酸二氢钾等量混合(用10%磷酸调pH值2.8)(24:76)为流动相,流速1.0 mL·min-1,检测波长254 nm,柱温30℃,结果:马钱子碱、士的宁的线性范围均为1～20 nag·L～,,.=0.999 9.低、中,高浓度士的宁平均加样回收率分别为(101.2±1.8)%,(99.2±1.3)%,(99.1±1.2)%(n=3);低、中、高浓度马钱子碱的加样回收率分别为(103.9±2.8)%,(100.4±0.4)%,(102.7±1.2)%(n=3).结论:本方法操作简便,是在药典方法基础上的改进,可用于控制马钱子总生物碱脂质体的质量.     

酮洛芬脂质体凝胶在大鼠体内的药物动力学及皮肤组织分布研究

目的：研究酮洛芬（KPF）脂质体凝胶在大鼠体内的药物动力学及其皮肤局部组织分布。方法：选择SD大鼠为动物模型,与KPF口服给药相对照,研究KPF脂质体凝胶局部用药后在血浆和皮肤中的体内药动学行为。结果：KPF脂质体凝胶大鼠局部给药后的血药浓度Cmax、AUC0→24分别为（1．255±0．54）μg·ml^-1和（59．388±3．76）μg·ml^-1·h,局部皮肤组织的Cmax、AUC0→24分别为（28．019±1．98）μg·ml^-1和（602．21±2．84）μg·ml^-1·h。与口服KPF相比,KPF脂质体凝胶降低了血液中的分布,而具有明显的皮肤蓄积能力（P〈0．05）。结论：KPF脂质体凝胶局部给药在获得较高的皮肤组织浓度的同时,避免了较高的血药浓度的不良反应,疗效优于口服．     

硫酸长春新碱空白脂质体的稳定性研究

目的考察三瓶装硫酸长春新碱脂质体中空白脂质体的物理、化学稳定性。方法采用高效液相色谱-蒸发光散射检测器(HPLC-ELSD)测定空白脂质体中氢化大豆磷脂(HSPC)的含量;采用粒度仪测定脂质体粒径;用阳离子树脂分离脂质体与游离药物,测定包封率。结果在4℃下,空白脂质体的理化性质未见明显变化,稳定性较好。结论硫酸长春新碱脂质体适合制成三瓶分装制剂,有利于提高药物稳定性。     

L-cysteine encapsulation in liposomes: Effect of phospholipids nature on entrapment efficiency and stability

Liposomal entrapment of L-cysteine (L-CySH) could be a solution to enhance its oxidative stability and its intracellular bioavailability for glutathione (GSH) synthesis. This study addresses the influence of different factors (i.e. pH value (6.3 vs 7.4), antioxidant agents (EDTA or tocopherol (TO))) and nature of phosphatidylcholine (PC) (Soybean PC (SPC) vs hydrogenated SPC (HSPC)) to formulate and optimize Large Unilamellar Vesicles (LUVs) of L-CySH composed of PC/Cholesterol/Phosphatidylglycerol (6 : 3 : 1). pH decrease (p =?0.0002) and substitution of SPC by HSPC (p <?0.001) reduced L-CySH oxidation. EE% (entrapment efficiency) varied from 0.98% ±?0.54 (SPC, pH 7.4) to 6.46% ±?1.37 (HSPC, pH 6.3) and was improved by decreasing pH (p =?0.011) and using HSPC (p <?0.0001). An immediate release of L-CySH was observed with SPC. On the contrary, with HSPC at pH 6.3, 42.0% ±?1.2 and 73.0% ±?1.7 remained encapsulated after 24 h at 25°C and 4°C, respectively. In conclusion, HSPC offering both stronger rigidity and lesser propensity for peroxidation led to optimize L-CySH liposomal stability.     

马钱子碱脂质体的大鼠离体透皮性能和兔皮肤刺激性研究

采用薄膜-超声分散法制备马钱子碱脂质体,并考察了其对大鼠离体皮肤的透过性能及对家兔皮肤的刺激性。结果表明,制品平均粒径(150±25)nm、包封率61%、载药量6%。体外透皮试验表明,与乳膏相比,制品透皮速率较慢,皮肤层中药物贮存量较高。兔皮肤刺激性试验表明,1日给予2次时对皮肤基本无刺激,但连续用药2周,则会产生水肿、溃疡等局部不良反应。     

酸性成纤维细胞生长因子阳离子脂质体在大鼠体内的药动学

采用pH梯度法制备了酸性成纤维细胞生长因子(aFGF)阳离子脂质体,建立了生物素-亲和素放大酶联免疫吸附测定(BA-ELISA)法检测大鼠血清中的药物浓度。结果显示,血清中的aFGF浓度在31.2～500 pg/ml范围内线性关系良好,回收率大于97%,日内、日间RSD<10%。大鼠分别尾静脉注射不同剂量(20、50和100 μg/kg)的aFGF阳离子脂质体和aFGF溶液,用以考察制品在大鼠体内的药动学行为。结果显示,低、中、高浓度的aFGF阳离子脂质体与aFGF溶液相比,阳离子脂质体组的消除半衰期(t_1/2)和平均滞留时间(MRT)均显著延长(P<0.05);阳离子脂质体组的药-时曲线下面积(AUC)呈现出剂量依赖性增长,并且高剂量组的AUC与高浓度aFGF溶液组相比有极显著差异(P<0.01)。本研究结果表明,aFGF阳离子脂质体延长了aFGF的体内存在时间,有效提高了aFGF的生物利用度。     

羟喜树碱脂质体的制备及在犬体内的药动学研究

采用溶剂注入-高压均质法制备羟喜树碱脂质体.结果显示,本品平均粒径为(182.5±5.6)nm,ζ电位为-(33.10±0.56)mV,包封率大于90%.以市售注射液为参比制剂,采用单剂量双周期交叉试验考察静脉给药后羟喜树碱脂质体在Beagle犬体内的药动学行为.结果表明,羟喜树碱经脂质体包裹后可维持较高的血药浓度,延长了药物在体内的消除时间.     

铂类抗肿瘤药物脂质体研究进展

综述了几种铂类抗肿瘤药（如顺铂、卡铂、奥沙利铂及其衍生物）脂质体的制备工艺、体内研究、临床应用等进展。     

Effect of Liposome Characteristics and Dose on the Pharmacokinetics of Liposomes Coated with Poly(amino acid)s

Long-circulating liposomes, such as PEG-liposomes, are frequently studied for drug delivery and diagnostic purposes. In our group, poly(amino acid) (PAA)-based coatings for long-circulating liposomes have been developed. These coatings provide liposomes with similar circulation times as compared to PEG-liposomes, but have the advantage of being enzymatically degradable. For PEG-liposomes it has been reported that circulation times are relatively independent of their physicochemical characteristics. In this study, the influence of factors such as PAA grafting density, cholesterol inclusion, surface charge, particle size, and lipid dose on the circulation kinetics of PAA-liposomes was evaluated after intravenous administration in rats. Prolonged circulation kinetics of PAA-liposomes can be maintained upon variation of liposome characteristics and the lipid dose given. However, the use of relatively high amounts of strongly charge-inducing lipids and a too large mean size is to be avoided. In conclusion, PAA-liposomes represent a versatile drug carrier system for a wide variety of applications.     

甘草提取物对唑吡坦在大鼠体内的药动学影响

目的 研究甘草提取物对唑吡坦在大鼠体内药动学的影响。方法 12只大鼠随机分为对照组与甘草组,分别予生理盐水和甘草提取物(0.5 g·kg^-1,qd)7 d后唑吡坦灌胃给药,按时间点连续采样,采用HPLC-FLU测定血药浓度。计算其主要药动学参数,并进行统计学分析。结果 合用甘草后,唑吡坦的tmax显著缩短(P<0.05),AUC0→8 h、AUC0→∞显著减小(P<0.05),CL/F显著增高(P<0.05),而Cmax和t1/2变化无统计学差异。结论 甘草提取物影响唑吡坦在大鼠体内的代谢,临床上两药合用应注意潜在的药物相互作用风险。     

Pharmacokinetics and Tissue Disposition in Monkeys of an Antisense Oligonucleotide Inhibitor of Ha-Ras Encapsulated in Stealth Liposomes

Purpose. This study examined the pharmacokinetics and tissue distribution of an antisense oligonucleotide ISIS 2503, formulated in stealth (pegylated) liposomes (encapsulated) or in phosphate-buffered saline (unencapsulated). Methods. Encapsulated or unencapsulated ISIS 2503 was administered to rhesus monkeys by intravenous infusion. The concentrations of ISIS 2503 and metabolites in blood, plasma, and tissue samples were determined by capillary gel electrophoresis. Results. Plasma concentrations of encapsulated ISIS 2503 decreased mono-exponentially after infusion with a mean half-life of 57.8 hours. In contrast, the concentration of unencapsulated ISIS 2503 in plasma decreased rapidly with a mean half-life of 1.07 hours. Both encapsulated and unencapsulated ISIS 2503 distributed widely into tissues. Encapsulated ISIS 2503 distributed primarily to the reticulo-endothelial system and there were few metabolites observed. In contrast, unencapsulated ISIS 2503 distributed rapidly to tissue with highest concentration seen in kidney and liver. Nuclease-mediated metabolism was extensive for unencapsulated oligonucleotide in plasma and tissues. Conclusions. The data suggest that stealth liposomes protect ISIS 2503 from nucleases in blood and tissues, slow tissue uptake, and slow the rate of clearance from the systemic circulation. These attributes may make these formulations attractive for delivering oligonucleotides to sites with increased vasculature permeability such as tumors or sites of inflammation.     

重组人生长激素缓释微球.Ⅱ.大鼠体内的药物动力学研究

考察重组人生长激素（rhGH）可生物降解微球在动物体内的缓释效果，探讨蛋白稳定剂对微球体内药物动力学行为的影响。大鼠皮下注射rhGH-PLGA微球后，利用放射免疫吸附分析法测定血药浓度。结果表明，rhGH-PLGA微球具有明显的缓释作用，给药后d30，动物体内的rhGH浓度仍维持在正常生长激素水平之上。而大鼠同等剂量给予rhGH溶液24h后，其体内的生长激素浓度即恢复至正常水平。微球内水相中加入泊洛沙姆407（F127），使rhGH的相对生物利用度增加约12．5％，进一步证实了F127对rhGH具有稳定作用。