穿琥宁肠溶胶囊在犬体内的药物动力学及绝对生物利用度

目的　研究穿琥宁肠溶胶囊在犬体内的药物动力学及绝对生物利用度。方法　家犬 6只 ,随机分为 2组 ,采用单剂量交叉给药方案 ,分别给犬单剂量静脉注射或口服穿琥宁肠溶胶囊 ,用HPLC法测定给药后的血中药物浓度 ,3p97药动学程序处理。结果　穿琥宁肠溶胶囊的药 -时数据符合二室模型 ,Cmax为 2 4 .3μg·ml-1,Tmax为 1.2 6h ,AUC(0→∞ ) 为 2 92 84 μg·ml-1,绝对生物利用度为 30 .0 3%。结论　穿琥宁肠溶胶囊有较好的生物利用度     

穿琥宁中空栓在兔体内的药物动力学及绝对生物利用度

目的：研究穿琥宁中空栓在兔体内的药物动力学及绝对生物利用度。方法：取健康家兔30只，随机分为3组。第1组为静脉注射组；第2组为聚乙二醇300穿琥宁申空栓组；第3组为1，2丙二醇穿琥宁中空栓组，分别静脉注射穿琥宁100mg或直肠给予穿琥宁中空栓1枚。用HPLC法测定血药浓度。按统计矩的非隔室动力学理论计算药物动力学参数。结果：聚乙二醇300穿琥宁中空栓和1，2丙二醇穿琥宁中空栓的Cmax分别为（37．4±5．3）和（20．2±4．6）μg·ml^-1；AUC（0-inf）分别为（2885．92±214．578）和（1960．98±111．194）μg·min·ml^-1；绝对生物利用度分别为18．33％和12．45％。结论：聚乙二醇300穿琥宁中空栓组和1，2丙二醇穿琥宁中空栓组的Cmax和AUC（0-inf）有统计学差异。     

冰片对大鼠经鼻腔给药灯盏花素体内药动学的影响

目的:探索冰片对大鼠经鼻腔给药灯盏花素体内药代动力学的影响。方法:采用同位素标记法125I检测实验大鼠经过尾静脉注射、单纯鼻腔给药和鼻腔给药联合冰片三种途径摄入0.4mg/kg灯盏花素以后的药代动力学,测定1、5、10、30、60、90、120、150、180、210、270min的血浆中灯盏乙素的浓度,绘制药时曲线并比较三种途径的药代动力学参数。结果:经鼻腔给药联合冰片组大鼠的tmax为22min短于单纯鼻腔给药组的tmax30min,差异有统计学意义(t=5.73,P=0.025);经鼻腔联合冰片组和单纯鼻腔给药组的Cmax分别为0.55、0.52μg/mL,绝对生物利用度分别为53.21%和53.71%,差异没有统计学意义。结论:冰片可以在一定程度上影响大鼠经鼻腔灯盏花素给药,使其血浆灯盏乙素浓度的达峰时间缩短,但是对灯盏乙素的绝对生物利用度没有明显影响,可以为灯盏花素新制剂的研究提供新方向。     

RP-HPLC法测定人血浆中穿琥宁含量及药代动力学研究

目的:研究穿琥宁在人体内的药代动力学过程并建立人生物样品的高效液相色谱方法。方法:采用液-液萃取的方法从生物样品中提取出穿琥宁后用Diaminsil-C18(2)色谱柱(250 mm×4.6 mm,5μm)柱进行分离,采用的流动相为:乙腈-磷酸盐缓冲液[0.5 g.L-1磷酸二氢钾,用磷酸调节pH至2.5(±0.05)](43∶57,v/v)。结果:穿琥宁在人体内静脉给药200 mg后药代动力学符合二室模型,统计距参数为:Cmax为(9.796±2.306)μg.mL-1、Tmax(1.382±0.231)h、T1/2z(1.678±0.509)h。结论:此方法快捷、灵敏、简便,适合于穿琥宁的药代动力学研究。     

小檗碱静脉注射及鼻腔给予在大鼠血浆与海马中的药代动力学研究

初步比较小檗碱静脉注射及鼻腔给予在大鼠血浆和海马组织中的药代动力学参数的差别。120只大鼠随机分为小檗碱静脉注射6 mg/kg和鼻腔给予9 mg/kg组,分别在给药后12个时间点采血和分离海马组织,采用反相高效液相色谱内标法,检测血浆和海马给织中小檗碱含量,并利用DAS软件计算其药代动力学参数。结果表明,小檗碱血药浓度-时间曲线经拟合二房室模型,鼻腔给药的生物利用度3.05,在海马中的直接转运率为52.663%     

灯盏花素在小鼠体内药物动力学研究

目的:研究灯盏花素在小鼠体内的药物动力学和绝对生物利用度。方法:采用固相萃取 高效液相色谱(SPE HPLC)法,测定小鼠静脉注射灯盏花素5 0mg·kg-1和灌胃15 0mg·kg-1后血浆灯盏乙素浓度,3p97程序处理数据。结果:小鼠静注灯盏花素后灯盏乙素的血浓 时间变化符合三房室模型,AUC、C0 和T1 2 β分别为12 .97±3.5 5mg·L-1·h、132 .2 3±39.90mg·L-1和4 .0 4±1.2 9h。灌胃后药物吸收很快,但血浓低。采用非房室模型法计算AUC为1.97±0 .5 3mg·L-1·h ,T1 2Ke 为3.4 1±1.2 3h。绝对生物利用度为5 .0 5 %。结论:灯盏花素经静注在小鼠体内的药代动力学符合三室模型。灌胃给药吸收快,但吸收差,绝对生物利用度低,且药时曲线变化不规则。     

齐墩果酸磷酸酯二钠盐的药物动力学与生物利用度研究

采用高效液相色谱法对齐墩果酸磷酸酯二钠盐 (disodiumoleanolicacidphosphate,以下简称为OLANa2 )进行了大鼠体内的药物动力学与生物利用度研究。大鼠静脉注射 3种不同剂量 ( 4 0、5 0、6 0mg/kg)的OLANa2 注射液后 ,其药物动力学行为均符合二室开放模型特征 ,且在实验剂量范围内其药时过程为线性动力学。大鼠灌胃及肝门静脉给药后 ,其药时过程符合单室开放一级吸收模型特征。大鼠经灌胃、肝门静脉、颈静脉交叉给药后 ,灌胃的绝对生物利用度为 2 2 0 3% ,肝门静脉注射的绝对生物利用度为 88 89% ,胃肠道代谢或未吸收部分共为 6 6 9%。     

三七总皂苷鼻腔给药的药代动力学与药效学

目的研究三七总皂苷鼻腔用粉雾剂以混悬液形式给药后在大鼠体内的药代动力学过程及对心脑血管疾病的保护作用。方法HPLC测定三七总皂苷混悬液大鼠鼻腔给药后血样中人参皂苷Rg1的浓度，考察药物在体内的动力学过程，并计算其绝对生物利用度；结扎SD大鼠的左冠状动脉建立急性缺血性心肌梗死模型，夹闭沙鼠的双侧颈总动脉建立脑缺血再灌注模型，考察三七总皂苷混悬液对心脑血管疾病的保护作用。结果三七总皂苷混悬液鼻腔给药后，Rg1在大鼠体内的过程符合二室模型，其绝对生物利用度为103.56％；对大鼠急性缺血性心肌梗死及沙鼠脑缺血再灌注所引起的脑水肿和脑卒中症状均具有明显的缓解作用，且呈剂量依赖性，剂量越高，保护作用越强。结论药代动力学和药效学结果证明，三七总皂苷鼻腔给药制剂具有很好的开发前景。     

大黄酸在大鼠和比格犬体内的吸收动力学研究

目的：研究中药大黄的活性蒽醌单体大黄酸（rhein）在SD大鼠和Beagle犬体内的吸收动力学特征,为临床的进一步研究提供基础参数和依据。方法：采用HPLC-荧光检测法分别测定SD大鼠和Beagle犬在灌胃及静脉注射两种给药途径下单次给予不同剂量的大黄酸药物后,两种动物血浆样品中的大黄酸经时曲线过程并计算相应的药代动力学参数及绝对生物利用度。结果：SD大鼠灌胃及静脉注射高、中、低剂量大黄酸后,AUC与剂量间呈一定的线性关系（r〉0.99）,灌胃及静脉注射3个剂量下的半衰期结果相似。在上述研究范围内大黄酸在大鼠体内的药代动力学行为近似是线性的。用面积法,算得高、中、低3个剂量下大黄酸在大鼠体内的绝对生物利用度分别为16.4%、23.8%、19.4%。对6只Beagle犬进行随机交叉试验,静脉注射大黄酸真溶液（0.4mg/kg）和灌胃大黄酸混悬液（20mg/kg）,算得静注及灌胃后药物的消除半衰期分别为（1.77±0.93）、（3.25±0.80）h,Beagle犬体内的绝对生物利用度为（49.7±7.4）%。对Beagle犬组（6只）和SD大鼠灌胃3剂量组（18只）各只动物生物利用度进行方差分析,结果显示差异具有统计学意义（P〈0.01）。结论：大黄酸在不同动物间吸收存在一定的种属差异,吸收程度在Bea-gle犬体内略高于在大鼠体内。     

姜黄素在大鼠体内药代动力学和生物利用度研究

目的研究姜黄素不同给药途径在大鼠体内的药代动力学和绝对生物利用度。方法建立大鼠血浆中姜黄素的HPLC检测方法。考察大鼠分别经灌胃ig(200 mg·kg-1)、ip腹腔注射(20 mg·kg-1)、舌下静脉iv(10 mg·kg-1)给予姜黄素后血药浓度变化。用DAS2.0软件计算药动学参数,根据腹腔注射、灌胃和静脉给药药-时曲线下面积AUC(0-∞)和给药剂量,计算腹腔注射和口服姜黄素的绝对生物利用度。结果姜黄素浓度在0.05～6.00 mg·L-1范围内线性关系良好(r=0.9998);定量下限为0.05 mg·L-1;低(0.10 mg·L-1)、中(1.00 mg·L-1)、高(4.00 mg·L-1)3个浓度的回收率分别为(99.29±5.40)%、(104.21±4.72)%和(99.83±1.97)%;日内RSD分别为4.49%、3.90%和1.72%,日间RSD分别为4.61%、4.27%和2.00%。大鼠经灌胃、腹腔注射和静脉注射姜黄素后,姜黄素在大鼠体内的代谢过程均符合二室模型,消除半衰期分别为(159.28±18.12)、(90.79±11.55)和(11.96±2.64)min;AUC(0-∞)分别为(86.36±12.90)、(73.39±8.72)、(104.62±11.89)mg.min.L-1。按剂量折算,姜黄素经腹腔注射给药的绝对生物利用度为35.07%,灌胃给药的绝对生物利用度为4.13%。结论姜黄素经不同途径给药在大鼠体内的药代动力学过程相似,腹腔注射给药的绝对生物利用度较高,口服生物利用度低。     

穿琥宁注射液在6种输液中的稳定性考察

研究穿琥宁注射液在６种常用输液中的稳定性。方法：应用紫外分光光度计、酸度计、注射液微粒分析仪分别考察穿琥宁注射液与６种输液配伍后在不同温度下的外观、含量、ｐＨ、微粒及紫外吸收光谱的变化。结果：穿琥宁注射液与６种输液配伍后外观、ｐＨ、微粒、含量、紫外吸收光谱均无显著变化。结论：穿琥宁注射液可与６种输液配伍应用。     

穿琥宁注射液与24种药物配伍的稳定性考察

目的：研究穿琥宁注射液与临床常用２４种药物配伍的稳定性,方法：考察穿琥宁注射液与２４种药物在室温下配伍后外观,ｐＨ微粒和紫外吸收度,结果：穿琥宁注射液与庆大霉素,丁氨卡那霉素,环丙沙星,氧氟沙星配伍产生沉淀,与ＶｉｔＣ,ＶｉｔＢ６,ＡＴＰ辅酶Ａ,胞二磷胆碱,氨茶碱,氢化考的松,地塞米松,三氮唑核苷,阿昔洛韦,双黄连,青霉素钠,氨苄西林钠,红霉素,头孢唑啉钠,头孢哌酮钠,头孢曲松钠,头孢呋辛钠,甲硝     

注射用穿琥宁与小儿常用输液配伍的稳定性考察

目的 考察常温下注射用穿琥宁与3种小儿常用输液配伍的稳定性.方法 采用紫外分光光度法测定配伍后0～8 h内穿琥宁含量的变化,同时观察配伍液的外观、pH值及紫外吸收光谱的变化.结果 室温下8h内,注射用穿琥宁与3种小儿常用输液配伍后外观、pH值及紫外吸收光谱均无显著变化.结论 注射用穿琥宁可与3种小儿常用输液配伍应用.     

注射用穿琥宁与4种抗生素配伍的稳定性考察

目的：研究注射用穿琥宁与4种抗生素配伍的稳定性。方法：考察穿琥宁与4种抗生素在25℃和37℃两种温度条件下6h内配伍后外观、pH值、微粒数和紫外吸收度。结果：在上述条件下,注射用穿琥宁与头孢唑林钠、头孢拉定、舒巴坦/头孢哌酮、阿洛西林钠的配伍液外观、pH值、微粒数、紫外吸收度均无明显变化。结论：25℃及37℃条件下6h内,注射用穿琥宁可与头孢唑林钠、头孢拉定、舒巴坦/头孢哌酮、阿洛西林钠配伍使用。     

Effect of borneol on the distribution of gastrodin to the brain in mice via oral administration

Both borneol and gastrodin are bioactive substances derived from traditional Chinese medicine. In this paper, the effect of borneol on the distribution of gastrodin to the brain in mice via oral administration was investigated. Gastrodin concentrations in plasma and gastrodigenin (active metabolite of gastrodin) concentrations in the brain of mice were determined by reversed-phase high-performance liquid chromatography, after intragastric administration of gastrodin (200 mg kg(-1)) alone or combined with different doses (200, 400 and 600 mg kg(-1)) of borneol simultaneously or the same dose (400 mg kg(-1)) of borneol given 20 and 40 min beforehand, respectively. Compared with the administration of gastrodin alone, gastrodin coadministrated with borneol could have been rapidly absorbed from the gastrointestinal tract; the peak time of gastrodin in the plasma became shorter (5-15 vs. 30 min); the bioavailability of gastrodigenin in the brain was increased by 33.6-108.8%; and obvious brain-targeting effect was observed. The enhancing effect was attenuated when the dose of borneol was too high (600 mg kg(-1)), or the time interval between the administration of borneol and gastrodin was longer than 40 min. The results indicate that borneol can accelerate the absorption of gastrodin in the gastrointestinal tract and promote its distribution to the brain. Therefore, borneol is a promising promoter for oral brain-targeting drug delivery.     

HPLC determination of chondrosine in mouse blood plasma after intravenous or oral dose

The bioavailability of chondrosine was evaluated by its direct measurement as found in the blood plasma following removal of plasma proteins by perchloric acid. The postcolumn HPLC determination of chondrosine was performed on an SCX column (6 mm i.d.x 150 mm), 0.35 mol/l boric acid (pH 5.2 adjusted by 0.1 mol/l NaOH) as an eluent (0.9 ml/min), 0.5% 2-cyanoacetamide and 1.0 M NaOH as fluorogenic reagents (0.25 ml/min each) with a fluorescence detector (ex. 331nm, em. 383nm). Two separate animal studies were conducted. In study 1, adult male ddY mice (n=6) received i.v. chondrosine (1.0 mg/kg body weight) and the plasma samples were collected. In the second study, 6 adult male ddY mice received p.o. chondrosine (400 mg/kg body weight) and the plasma samples were collected. Blood plasma samples were deproteinized by perchloric acid, analyzed and the bioavailability of chondrosine was determined. Twenty five to fifty microliters of blood plasma were required for the assay. Chondrosine was absorbed after oral administration with two phases having two maximum values, 7.8+/-5.4 and 4.0+/-1.9 at 15 microg/ml and 120 min, respectively; it disappeared from the blood flow very quickly after intravenous administration. This study provides the first report of the bioavailability of orally administered chondrosine in mice.     

Effect of borneol on the distribution of gastrodin to the brain in mice via oral administration

Both borneol and gastrodin are bioactive substances derived from traditional Chinese medicine. In this paper, the effect of borneol on the distribution of gastrodin to the brain in mice via oral administration was investigated. Gastrodin concentrations in plasma and gastrodigenin (active metabolite of gastrodin) concentrations in the brain of mice were determined by reversed-phase high-performance liquid chromatography, after intragastric administration of gastrodin (200 mg kg^{? 1}) alone or combined with different doses (200, 400 and 600 mg kg^{? 1}) of borneol simultaneously or the same dose (400 mg kg^{? 1}) of borneol given 20 and 40 min beforehand, respectively. Compared with the administration of gastrodin alone, gastrodin coadministrated with borneol could have been rapidly absorbed from the gastrointestinal tract; the peak time of gastrodin in the plasma became shorter (5–15 vs. 30 min); the bioavailability of gastrodigenin in the brain was increased by 33.6–108.8%; and obvious brain-targeting effect was observed. The enhancing effect was attenuated when the dose of borneol was too high (600 mg kg^{? 1}), or the time interval between the administration of borneol and gastrodin was longer than 40 min. The results indicate that borneol can accelerate the absorption of gastrodin in the gastrointestinal tract and promote its distribution to the brain. Therefore, borneol is a promising promoter for oral brain-targeting drug delivery.     

Pharmacokinetics of bendamustin (Cytostasan) in B6D2F1-mice]

The pharmacokinetics of bendamustine, (1; Cytostasan), an alkylating antineoplastic agent of the N-lost group, was investigated in B6D2F1 mice. After i.v. injection of the maximally tolerated dose of 50 mg/kg a rapid decrease of the unchanged drug in plasma (MRT 21.9 min) and slowly decreasing levels of mono-, dihydroxy and beta-hydroxy-1 were observed. Variations of the age of the animals as well as of the dose administered did not alter the short MRT of 1. 1 is excreted via the kidneys to a considerable extent showing a similar metabolite pattern in urine as in plasma. The absorption of the drug from the gastrointestinal tract is incomplete resulting in an absolute bioavailability of about 40%.     

Enhanced oral bioavailability of paclitaxel by D-alpha-tocopheryl polyethylene glycol 400 succinate in mice

Paclitaxel is widely used to treat several types of solid tumors. The commercially available paclitaxel formulation contains Cremophor/ethanol as solubilizers. This study evaluated the effects of D-alpha-tocopheryl polyethylene glycol 400 succinate (TPGS 400) on the oral absorption of paclitaxel in mice. Mice were given an intravenous (18mg/kg) or oral (100mg/kg) dose of paclitaxel solubilized in Cremophor/ethanol or in TPGS 400/ethanol formulations. Paclitaxel plasma concentrations and pharmacokinetic parameters were determined. The maximal plasma concentrations of paclitaxel after an oral dose were 1.77+/-0.17 and 3.39+/-0.49microg/ml for Cremophor/ethanol and TPGS 400/ethanol formulations, respectively, with a similar time at 40-47min to reach the maximal plasma concentrations. The oral bioavailability of paclitaxel in TPGS 400/ethanol (7.8%) was 3-fold higher than that in Cremophor/ethanol (2.5%). On the other hand, the plasma pharmacokinetic profiles of intravenous paclitaxel demonstrated a superimposition for the two formulations. Furthermore, TPGS 400 concentration-dependently increased the intracellular retention of Rhodamine 123 in Caco-2 cells and enhanced paclitaxel permeability in monolayer Caco-2 cultures. TPGS 400 at concentrations up to 1mM did not inhibit testosterone 6beta-hydroxylase, a cytochrome P450 isozyme 3A in liver microsomes metabolizing paclitaxel. Our results indicated that TPGS 400 enhances the oral bioavailability of paclitaxel in mice and the enhancement may result from an increase in intestinal absorption of paclitaxel.     

奥美拉唑肠溶胶囊的人体相对生物利用度与生物等效性研究

目的建立测定血浆奥美拉唑浓度的高效液相色谱（HPLC）法,研究奥美拉唑肠溶胶囊的相对生物利用度及其生物等效性。方法按两制剂双周期自身对照交叉试验设计, 男性健康志愿者20例,分别单剂量口服2种国产奥美拉唑肠溶胶囊,用HPLC法测定血药浓度,计算药动学参数,并评价两种制剂的生物等效性。结果口服奥美拉唑肠溶胶囊参比制剂及受试制剂40 mg后的主要药动学参数：峰浓度（Cmax）分别为（906.01±589.55）和（875.87±662.95） ng•mL 1 ;达峰时间（tmax）分别为（2.21±0. 88）和（2.07±0. 87） h;血药浓度 时间曲线下面积（AUC0 12）分别为（1 778.70±1 164.11）和（1 834.25±1 342.25） ng•h•mL 1;半衰期（t1/2Ke）分别为（ 0.96 ±0.25）和（0.85 ±0.18） h。受试制剂对参比制剂平均相对生物利用度F0→12为（104.02 ±13.60 ）%。结论该两种奥美拉唑胶囊生物等效。