头孢羟氨苄咀嚼片的人体生物等效性

目的：评价头孢羟氨苄咀嚼片与参比片剂在人体内生物等效性。方法：采用随机交叉试验设计，20名健康男性受试者分别口服单剂量受试制剂与参比制剂500mg，HPLC法测定血浆中头孢羟氨苄的浓度，用DAS1．0统计软件计算药动学参数并进行生物等效性评价。结果：受试制剂与参比制剂的已。分别为（19．2±2．3）mg·L^-1和（18．4±2．7）mg·L^-1,tmax分别为（0．95±0．22）h和（1．3±0．4）h，t1/2分别为（1．78±0．14）h和（1．73±0．09）h，AUC（0→10）分别为（53．3±7．5）mg·h·L^-1和（54．0±7．4）mg·h·L^-1,AUC（0→∞）分别为（54．4±7．9）mg·h·L^-1和（55．1±7．7）mg·h·L^-1。受试制剂相对于参比制剂的生物利用度为（99．0±7．0）％。结论：两制剂具有生物等效性。     

兰索拉唑片人体药代动力学和生物等效性研究

目的：评价兰索拉唑片（受试制剂）与兰索拉唑胶囊（参比制剂）的人体生物等效性。方法：血浆样品采用液-液萃取处理，HPLC法测定。18名健康受试者随机分组、自身交叉口服单剂量受试制剂和参比制剂进行生物等效性评价。结果：受试制剂的AUC0^1，AUC0^∞，Cmax，tmax，t1／2分别为4．70±0．57mg·h^-1·L^-1，5．10±0．58mg·h·L^-1，1．33±0．10mg·L^-1，2．5±0．1h，2．2±0．4h。参比制剂的AUC0^1，AUC0^∞，Cmat，tmax，t1／2分别为4．62±0．59mg·h·L^-1，4．98±0．63mg·h·L^-1，1．32±0．08mg·L^-1，2．5±0．1h，2．0±0．2h，受试制剂相对参比制剂的人体相对生物利用度F1为（102．2±10．1）％，R为（103.1±9．2）％。受试制剂相对参比制剂的主要药动学参数经交叉试验方差分析示无统计学差异（P均〉0．05），两制剂的AUC0^1，AUC0^∞，Cmax，经双单侧t检验示90％置信区间均位于有效置信区间80％-125％范围内。结论：受试制剂和参比制剂具有生物等效性。     

麦考酚酸酯分散片在健康人体的药动学和生物等效性

目的:研究麦考酚酸酯(MMF)国产分散片和进口胶囊在健康人体的药动学及其生物等效性。方法:采用随机自身对照双周期交叉试验设计,18名男性健康志愿者口服MMF分散片或胶囊各1．0 g,用反相高效液相色谱一紫外检测法测定MMF的活性代谢产物麦考酚酸(MPA)的血药浓度,用非房室模型计算MPA的药动学参数,用方差分析和双单侧t检验评价2种制剂的生物等效性。结果:MMF分散片与胶囊麦考酚酸的药动学参数如下:t_(max)分别为(0．62±s 0．21),(0．74±0．23)h;c_(max)分别为(27±5), (28±6)mg·L~(-1);AUC0～36分别为(51±9),(49±9)mg·h·L~(-1);t1/2分别为(13．7±2．5),(13．9±2．5)h。国产麦考酚酸酯分散片中麦考酚酸相对于胶囊的相对生物利用度为(104±9)％,2种制剂的主要药动学参数经统计学检验,两者差异无显著意义(P＞0．05)。结论:2种制剂在人体内生物等效。     

氟康唑口服液人体相对生物利用度和生物等效性

目的：考察氟康唑新制刺氟康唑口服液与参比制刑氟康唑胶囊的人体相对生物利用度，并作出生物等效性评价。方法：按照两制剂两周期随机交叉设计，20名男性健康志愿者单剂量口服试验制剂氟康唑口服液和参比制剂氟康唑胶囊150mg。采用HPLC-紫外法测定血浆氟康唑浓度，并进行统计学分析。结果：单剂量口服150mg的氟康唑试验和参比制剂，测得AUCL（0→120）分别为（150．6±23．6）mg·h·L^-1和（150．6±18．6）mg·h·L^-1,AUC（0→∞）分别为（163．6±27．4）mg·h·L^-1和（162．2±21．4）mg·h·L^-1；Cmax分别为（3．8±0．5）mg·L^-1和（3．6±0．4）mg·L^-1；tmax分别为（1．9±1．4）h和（2．4±1．3）h。用药时曲线下面积AUC（0→120）计算，20名健康志愿者单剂量口服氟康唑口服液（试验制剂）相对生物利用度为（102．0±24．3）％。结论：两种制剂的AUC和Cmax数值经对数转换后均落在置信区间范围内，说明混悬剂与参比片生物等效。     

吗替麦考酚酯分散片药动学与相对生物利用度研究

目的评价吗替麦考酚酯分散片的药动学与人体相对生物利用度。方法将18例健康男性受试者随机平均分为两组,双周期交叉口服吗替麦考酚酯胶囊或分散片1 g。采用高效液相色谱法测定血药浓度［固定相: 日本岛津C18色谱柱(150 mm ×4.6 mm,5 μm)；流动相:10 mmol·L 1醋酸铵(磷酸调节pH值至4.0)－甲醇－乙腈 (35：25：40)；柱温: 40 ℃；流速: 1 mL·min 1；检测波长: 303 nm］,计算药动学参数并判断两种制剂的生物等效性。结果吗替麦考酚酯胶囊和分散片的主要药动学参数分别 : tmax 为(0.50±0.29)和(0.49±0.17) h, Cmax 分别为(36±5)和(38± 7) mg·L 1, t1/2 分别为(14±5)和(13±8) h, AUC0～24 分别为(62±10)和(61±10) mg·h 1·L 1, AUC0～∞分别为(83±23)和(78±15) mg·h 1·L 1。吗替麦考酚酯分散片平均相对生物利用度为(99±10)%。结论吗替麦考酚酯分散片和胶囊具有生物等效性。     

吗替麦考酚酯胶囊人体生物等效性研究

目的:研究2种吗替麦考酚酯胶囊的人体生物等效性。方法:18名受试者随机、交叉、单剂量分别口服吗替麦考酚酯胶囊受试制剂(国产)和参比制剂(进口)1000mg。血药浓度采用反相高效液相色谱法测定;计算药动学参数并评价生物等效性。结果:受试制剂与参比制剂的主要药动学参数Cmax分别为(26.38±9.55)、(25.84±12.08)μg·mL-1,tmax分别为(0.79±0.40)、(0.94±0.59)h,t1/2分别为(18.01±7.65)、(15.62±8.50)h,AUC0～48分别为(54.69±15.58)、(51.68±12.36)μg.h.mL-1,AUC0～∞分别为(61.10±17.06)、(57.99±17.21)μg.h.mL-1。受试制剂的相对生物利用度为(107.22±25.39)%。结论:国产与进口吗替麦考酚酯胶囊生物等效。     

吗替麦考酚酯软胶囊的药动学及生物等效性研究

目的:研究吗替麦考酚酯软胶囊与吗替麦考酚酯胶囊在健康人体内的相对生物利用度及药动学,评价2种制剂的生物等效性。方法:采用双周期随机交叉设计,20名男性健康志愿者单剂量口服试验软胶囊或参比胶囊4粒(每粒0.25g),以高效液相色谱法测定血浆中霉酚酸(MPA)浓度。运用DAS2.0软件处理血药浓度数据和计算药动学参数,对2种制剂做出生物等效性评价。结果:受试者口服1.0g吗替麦考酚酯软胶囊试验药或参比胶囊,其AUC0→t分别为(69.95±14.13)、(66.95±19.05)μg·h·mL-1,AUC0→∞分别为(85.18±20.51)、(77.39±23.78)μg·h·mL-1,Cmax分别为(31.26±13.09)、(31.90±14.45)μg·mL-1,tmax分别为(0.875±0.358)、(0.775±0.291)h,t1/2分别为(20.342±12.546)、(18.837±11.579)h。20名健康志愿者单剂量口服吗替麦考酚酯软胶囊试验药的相对生物利用度为(109.6±26.9)%。结论:试验软胶囊与参比胶囊具有生物等效性。     

国产苯磺酸氨氯地平片的生物等效性

目的：研究国产和进口苯磺酸氨氯地平片在健康人体的相时生物利用度和生物等效性。方法：采用两制剂双周期交叉试验设计。20名男性健康志愿者随机分别服用10mg苯磺酸氨氯地平试验药（国产）或时照药（进口），采用LC-MS测定血浆中氨氯地平质量浓度。并计算药动学参数和相对生物利用度，据此时两种制剂作出等效性评价。结果：单剂量口服10mg苯磺酸氨氯地平试验药和对照药的药动学参数：AUC0-120分别为（306．0±60．7）μg·h·L^-1和（315．1±62．7）／μg·h·L^-1；AUC0-∞。分别为（330．3±59．8）μg·h·L^-1和（341．7±67．2）μg·h·L^-1。分别为（7．6±1．7）／μg·L^-1和（7．8±1．6）μg·L^-1；分别为（7．7±2．2）h和（7．4±2．1）h；t1.2分别为（35．4±6．3）h和（36．4±5．1）h；国产苯磺酸氨氯地平片的相时生物利用度为（98．3％±13．2％）（F0-120）和（98．0％±12．5％）（F0-∞）。结论：经统计学分析，两种制剂具有生物等效性。     

3×3拉丁方设计评价国产麦考酚吗乙酯片、胶囊与其进口制剂的生物等效性

目的 3×3拉丁方研究国产麦考酚吗乙酯片剂、胶囊剂与进口麦考酚吗乙酯胶囊（商品名：骁悉）的生物等效性.方法 24名健康男性志愿者随机交叉单剂量口服国产麦考酚吗乙酯片剂、胶囊剂和进口麦考酚吗乙酯胶囊500 mg，以HPLC法测定血药浓度，计算各药动学参数和相对生物利用度，并以WinNonlin程序计算药动学参数，评价生物等效性.结果 国产麦考酚吗乙酯片剂、胶囊和进口麦考酚吗乙酯胶囊药-时曲线符合线性动力学-室开放模型，AUC0→48分别是（39.74±8.61）、（38.06±9.01）和（36.21±9.17）mg·h·L^-1 AUC0→∞：（44.02±10.62）、（40.91±9.54）和（39.82±9.21）mg·h·L^-1 ρmax：（20.19±9.63）、（17.42±6.03）和（18.48±7.06）mg·L^-1 tmax：（0.74±0.64）、（0.72±0.35）和（0.56±0.20）h t1/2：（13.43±4.58）、（12.20±3.08）和（13.59±5.40）h MRT：（14.95±5.85）、（13.42±2.83）和（14.40±5.47）h.结论 国产麦考酚吗乙酯片剂、胶囊与进口麦考酚吗乙酯胶囊具有生物等效性.     

替硝唑片的血浓度测定及相对生物利用度研究

目的：建立HPLC法测定替硝唑血浓度，用于人体生物等效性研究。方法：采用随机双交叉实验设计，20名健康受试者口服受试制剂和参比制剂1000mg，用HPLC法测定血浆中的替硝唑浓度。结果：受试制剂和参比制剂的A‰分别为（391．2±74．0）和（394．7±78．1）mg·h·L^-1；AUC0→∞分别为（420．4±80．7）和（426．1±85．8）mg·h·L^-1；Cmax分别为（20．2±4．9）和（20．0±4．5）mg·L^-1；tmax分别为（1．4±0．8）和（1．5±0．8）h；t1／2分别为（15．4±1．5）和（15．9±1．8）h。受试制剂的相对生物利用度为（99．6±8．3）％。经统计学分析，两制剂的AUC0→∞，Cmax,tmax，t1/2无显著性差异（P〉0．05）。结论：两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.

---

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.     

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.     

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.     

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.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.