盐酸吡格列酮胶囊的人体相对生物利用度

目的:评价盐酸吡格列酮胶囊的人体生物等效性.方法:18名男性健康志愿者随机交叉口服受试制剂盐酸吡格列酮胶囊和参比制剂盐酸吡格列酮片30 mg,采用反相高效液相色谱-紫外检测法测定血浆药物浓度.结果:受试制剂和参比制剂的Tmax分别为(1.9±0.5),(2.1±0.6)h;Cmax分别为(1 480.0±234.9),(1 436.5±206.4)μg·L-1;t1/2β分别为(6.0±1.4),(6.4±1.4)h;AUC0→24分别为(8 893.6±1979.9),(8893.2±1913.8)μg·L-1·h;AUC0→∞.分别为(9 706.4±2 394.5),(9928.3±2512.4)μg·L-1·h,盐酸吡格列酮胶囊的相对生物利用度为(101.4±17.5)%.结论:经统计学分析,盐酸吡格列酮胶囊与盐酸吡格列酮片具有生物等效性.     

格列喹酮片的药物动力学特征和生物等效性研究

目的 采用HPLC法研究格列喹酮片在健康人体内的药动学特征,并评价两制剂间的生物等效性.方法 22名健康男性志愿受试者随机交叉单剂量口服格列喹酮片(受试制剂)和糖适平(格列喹酮片,参比制剂)各60 mg,按设计时间点采集血样进行分析测定,绘制药-时曲线,计算相关的药动学参数.结果 受试者口服受试制剂和参比制剂后,血浆中格列喹酮的主要药动学参数Tmax分别为3.4±1.2、2.9±0.8 h;Cmax分别为1.341±0.404、1.465±0.476 μg·ml-1;t1/2分别为4.4±2.2、4.1±2.5 h;AUCo-t分别为7.312 4.2.203、7.183±2.483 μg·h·ml-1;AUCo-∞分别为8.336±2.515、8.002±2.527μg·h·ml-1.受试制剂的相对生物利用度为109.7%+38.1%.结论 结果表明两种制剂间无显著性差异,格列喹酮两种制剂间体内生物作用等效.     

格列喹酮片在健康人体生物等效性研究

目的:研究两种格列喹酮片在健康人体内的药动学特征,并评价两种制剂间的生物等效性。方法:18名健康男性志愿受试者随机交叉单剂量口服试验制剂和参比制剂60 mg,清洗期1周,采用HPLC法测定血清中格列喹酮浓度。结果:受试者口服试验制剂和参比制剂后,主要药代动力学参数如下:t1/2分别为(4.78±1.87),(4.19±1.57)h,tmax分别为(3.06±1.08),(3.28±1.49)h,Cmax分别为(0.87±0.35),(0.90±0.33)μg.mL-1,AUC0-t分别为(4.35±1.66),(4.62±1.23)μg.h.mL-1,AUC0-∞分别为(4.98±1.72),(5.19±1.42)μg.h.mL-1。试验制剂的相对生物利用度AUC0-t为(95.8±34.1)%,AUC0-∞为(97.7±29.4)%。结论:两种格列喹酮片为生物等效制剂。     

多潘立酮口腔崩解片在健康人体的生物等效性

目的观察多潘立酮口腔崩解片(胃动力药)在健康人体的生物等效性。方法22名健康受试者随机交叉单剂口服多潘立酮口腔崩解片剂及多潘立酮片剂后,用HPLC法测定多潘立酮血药浓度。结果2种制剂的Cmax分别为(40.43±12.89),(42.31±20.32)μg·mL-1;tmax分别为(0.84±0.29),(0.91±0.48)h;t1/2(ke)分别为(11.23±5.06),(10.13±4.02)h;AUC0-tn分别为(187.61±81.20),(189.07±97.69)μg·h·mL-1;AUC0-∞分别为(220.18±106.93)和(215.57±102.13)μg·h·mL-1;F0-tn、F0-∞分别为(102.61±16.41)%和(101.96±16.06)%。结论试验制剂和参比制剂具有生物等效性。     

格列喹酮在中国健康受试者体内的生物等效性研究

建立了测定格列喹酮血浆浓度的HPLC-荧光检测法,并对10名健康受试者随机交叉口服60 mg 格列喹酮胶囊和格列喹酮片后的药代动力学性质及其生物等效性进行了研究.以黄豆苷元二甲醚为内标,血浆样品经液-液萃取处理,荧光检测波长为315/410 nm;线性范围为50～2000 μg·l-1;本法的相对偏差(RE)< 4.5 %,日内RSD< 8.6 %,日间RSD< 5.2 %.格列喹酮胶囊和片剂的Tmax分别为2.70±0.48和2.35±0.75 h; Cmax分别为1532.3±481.8和1588.2±822.2 μg· l-1; t1/2分别为4.82±2.18和4.47±1.77 h; AUC0-t分别为6872.8±2575.1和6942.2±3747.8μμg· l-1· h.以AUC0-t计算相对生物利用度为103.8 %±15.7 %.统计分析表明,两种制剂在人体内生物等效.     

盐酸氨溴索口腔崩解片的人体生物等效性

目的研究受试药物盐酸氨溴索口腔崩解片和参比药物沐舒坦的人体生物等效性。方法19名健康男性志愿者口服单剂量受试药物或参比药物90 mg后,采用HPLC紫外法测定血浆中盐酸氨溴索浓度,用BAPP 2.0程序进行数据处理。结果参比药物沐舒坦和受试药物盐酸氨溴索口腔崩解片的ρmax分别为(168.60±46.40)和(168.34±41.16)μg.L-1,tmax分别为(2.2±0.7)和(1.6±0.5)h,t12ke分别为(6.31±1.99)和(6.21±1.75)h,AUC0→24分别为(1 115.81±342.11)和(1 171.65±372.37)μg.h.L-1。盐酸氨溴索口腔崩解片相对生物利用度为(106.2±19.6)%。结论ρmax和AUC0→24经自然对数转换后的方差分析与双单侧t检验表明,盐酸氨溴索口腔崩解片和沐舒坦吸收程度等效。tmax经非参数检验(Wilcoxon符号秩检验)表明,两者tmax有显著性差异,盐酸氨溴索口腔崩解片吸收速度明显快于沐舒坦。     

盐酸吡格列酮口腔崩解片的研制

目的研制盐酸吡格列酮口腔崩解片工艺。方法以崩解时限为主要指标筛选崩解剂微晶纤维素和交联聚维酮的配比,采用直接压片法制备盐酸吡格列酮口腔崩解片。结果使用微晶纤维素与交联聚维酮配比为8:2的复合崩解剂,其崩解时限均在20S以内,其他指标均符合规定。结论本制剂工艺简单,达到口腔崩解片的要求,质量稳定,成本较低,具有良好的市场前景和竞争力。     

厄贝沙坦口腔崩解片健康受试者体内的药动学及生物等效性研究

目的研究厄贝沙坦口腔崩解片在健康受试者体内的药动学和生物等效性.方法采用两制剂双周期随机交叉试验设计,20名男性健康受试者单剂量口服厄贝沙坦口腔崩解片或普通片剂300mg,HPLC测定血浆厄贝沙坦浓度.采用3P97程序进行数据处理.结果试验片剂与参比片剂的AUC0-36h分别为(18.2±4.9)μg·ml～·h和(17.2±4.1)μg·ml-1·h;Cmax分别为(2.8±0.6)μg·ml-1和(2.8±0.7)μg·ml-1;Tmax分别为(1.6±0.4)h和(1.5±0.4)h.结论两种制剂在人体内的血药浓度变化符合二室模型,主要药动学参数经统计学处理均无显著性差异.与普通片剂相比,厄贝沙坦口腔崩解片的相对生物利用度为95.8%±13.9%,两者具有生物等效性.     

格列吡嗪口崩片的人体生物等效性试验

目的研究格列吡嗪口崩片的人体相对生物利用度和生物等效性。方法健康志愿者20名,随机双交叉单剂量口服格列吡嗪口崩片和格列吡嗪片,剂量均为10 mg。分别于服药后24 h内多点抽取静脉血;用HPLC法测定血浆中格列吡嗪的浓度。用DAS药动学程序计算相对生物利用度并评价2种制剂生物等效性。结果单剂量口服试验和参比制剂后血浆中的格列吡嗪的ρmax分别为(930.16±171.63)和(915.12±126.11)μg.L-1;tmax分别为(3.05±0.94)和(3.85±1.39)h;AUC0→24分别为(8 220.93±1 162.94)和(7 927.13±1 158.82)μg.h.L-1;AUC0→∞分别为(8 821.76±1 323.28)和(8 303.96±1 239.24)μg.h.L-1。ρmax、AUC0→24和AUC0→∞的90%可信区间分别为94.82%~107.46%、99.76%~108.10%和101.93%~110.84%。结论试验与参比制剂的人体相对生物利用度为(104.5±12.0)%,两制剂具有生物学等效性。     

头孢克肟口腔崩解片在健康志愿者的生物等效性研究

目的：研究头孢克肟口腔崩解片与头孢克肟胶囊的人体生物等效性。方法：使用高效液相色谱法测定20名健康男性受试者按两制剂两周期的交叉试验设计口服单剂量500mg的参比制剂或受试制剂后血浆中不同时间点的头孢克肟浓度,使用DAS软件拟合计算药代动力学参数,评价两制剂的生物等效性。结果：受试制剂和参比制剂的头孢克肟达峰时间（tmax）分别为4.13±0.51、4.28±0.60h;峰浓度（Cmax）分别为4.23±1.11、4.03±1.07μg/mL;消除半衰期（t1/2ke）分别为3.33±0.26、3.29±0.32h。AUC0-24h分别为35.38±10.22、33.86±10.65μg/mL.h;AUC0-∞分别为36.11±10.08、34.60±10.52μg/mL.h。tmax经非参数秩和检验,受试制剂与参比制剂无显著性差异;Cmax、AUC0-24h、AUC0-∞经对数转换后做方差分析,受试制剂与参比制剂无显著性差异,双向单侧t检验结果表明受试制剂Cmax的90%可信限落在参比制剂70%-143%之间,受试制剂AUC的90%可信限落在参比制剂80%-125%之间;以头孢克肟的AUC0-24h计算,受试制剂头孢克肟片的相对生物利用度为（106.5±16.8）%。结论：两种制剂具有生物等效性。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.