盐酸伐昔洛韦泡腾片在人体内的生物等效性

目的考察两种盐酸伐昔洛韦片的人体生物等效性。方法采用双制剂双周期自身交叉对照的方法,将18名健康男性受试者随机分为两组,单剂量口服盐酸伐昔洛韦受试制剂和参比制剂各0.6 g;血浆中阿昔洛韦浓度用HPLC法测定,DAS软件计算药物动力学参数,并对其进行生物等效性评价。结果盐酸伐昔洛韦受试制剂和参比制剂的Cm ax分别为2.54±0.32、2.59±0.44μg.m l-1;Tm ax分别为2.28±0.31、2.22±0.26 h;AUC0→Tn分别为10.75±1.804、11.35±2.548μg.h.m l-1,AUC0→∞分别为11.49±2.06、12.09±2.757μg.h.m l-1;t1/2分别为2.55±0.69 h、2.67±0.76 h。按盐酸伐昔洛韦药-时曲线下0→Tn的面积计算,相对生物利用度为96.1%。结论盐酸伐昔洛韦受试制剂与参比制剂相比,AUC、Cm ax符合生物等效性要求,Tm ax比较差异无统计学意义,受试制剂和参比制剂具有生物等效性。     

替米沙坦片的人体生物等效性研究

目的:研究两种替米沙坦片的人体生物等效性。方法:20名健康男性受试者按照两制剂两周期的随机交叉试验设计,分别单剂量口服受试制剂和参比制剂80 mg,用HPLC-荧光法测定血浆中替米沙坦的浓度,用DAS1.0软件对所得药动学参数进行统计分析。结果:受试制剂和参比制剂在受试者体内的药动学参数如下:cm ax分别为(0.92±0.62)和(1.04±0.61)μg/m l;tm ax分别为(0.97±0.61)和(1.03±0.65)h;AUC0-96 h分别为(4.32±2.86)和(4.41±2.51)μg.h.m l-1;AUC0-∞分别为(4.60±3.08)和(4.59±2.64)μg.h.m l-1;t1/2分别为(24.38±10.50)和(21.31±6.81)h。tm ax、cm ax、AUC0-96 h、AUC0-∞在两制剂间均无显著性差异,双单侧t检验结果表明受试制剂cm ax的90%置信区间落在参比制剂70%~143%之间,受试制剂AUC的90%置信区间落在参比制剂80%~125%之间;受试制剂的相对生物利用度为(109.2±31.9)%。结论:两制剂具有生物等效性。     

奥沙普秦肠溶片HPLC测定法及其人体生物等效性研究

目的建立一种HPLC检测法,以测定人体血浆中奥沙普秦的药物浓度,并对两种奥沙普秦肠溶片生物等效性进行评价。方法18名健康受试者单剂量交叉口服400 mg奥沙普秦供试制剂或参比制剂后不同时间点采血,采用HPLC法测定其浓度,计算其药动学参数和相对生物利用度,评价两制剂的生物等效性。结果奥沙普秦供试制剂与参比制剂AUC0-240 h分别为(2852.86±871.00)和(2992.84±854.02)μg.L-1.h,实测Cm ax分别为(33.48±11.36)和(32.70±7.30)μg.L-1,实测Tm ax分别为(12.1±5.7)和(13.8±5.8)h,T12ke分别为(57.11±8.51)h和(60.98±7.97)h。两制剂主要药动学参数经统计学分析差异无显著性。结论该方法简便灵敏,两制剂具有生物等效性。     

头孢克肟片人体药代动力学和生物等效性研究

目的研究头孢克肟供试制剂和参比制剂的药代动力学和人体生物等效性。方法用HPLC法测定18名健康受试者随机交叉口服200mg头孢克肟后血药浓度,用3P97进行最佳模型拟合,并计算药代动力学参数。结果不同时间药物在血清中的浓度符合2室模型,计算所得的供试制剂和参比制剂之间的主要药代动力学参数如下:Cmax为2.56±0.69,2.32±0.63 mg·L-1;tmax为3.17±0.66,3.5±0.62h,;tl/2β为3.15±0.49,3.31±0.51 h;AUC0-∞为19.91±5.18,19.09±5.36 mg·h.L-1;供试制剂对参比制剂的生物利用度为(106.22±1 8.48)％。结论供试制剂和参比制剂具有生物等效性。     

2种司帕沙星胶囊人体生物利用度与生物等效性研究

目的:比较2种司帕沙星胶囊的人体药动学参数、生物利用度,评价二者的生物等效性。方法:22名男性健康志愿者随机交叉单剂量口服200mg受试制剂或参比制剂后,应用高效液相色谱法测定血浆中司帕沙星浓度,并利用3p97程序计算药动学参数及评价二者生物等效性。结果:受试制剂与参比制剂体内药-时曲线符合二室模型,Cm ax分别为(0.85±0.23)、(0.90±0.27)μg.mL-1,tm ax分别为(5.59±2.28)、(4.95±1.17)h,AUC0~120分别为(27.92±6.09)、(29.65±8.49)μg.h.mL-1,AUC0~∞分别为(29.95±6.51)、(31.74±9.38)μg.h.mL-1。受试制剂相对生物利用度为(97.47±18.32)%。结论:受试制剂与参比制剂具有生物等效性。     

替硝唑片在健康人体的生物等效性研究

目的研究替硝唑片在健康人体内的相对生物利用度和生物等效性。方法 18名健康成年男性志愿者随机分为2组,采用自身交叉试验设计,单剂量口服1.0 g替硝唑片后,用高效液相色谱法测定血浆中药物浓度。结果替硝唑在0.50~60.11μg/m l浓度范围内线性良好(r=0.999 9),平均回收率99.7%~105.1%,日内和日间RSD均<3%。替硝唑试验制剂和参比制剂的主要药代动力学参数:Tm ax分别为(1.39±0.99)h和(2.00±1.39)h;Cm ax分别为:(25.43±5.62)μg/m l和(21.53±4.26)μg/m l;AUC0→60分别为(503.47±92.97)μg.h.m l-1和(468.83±87.49)μg.h.m l-1;AUC0→∞分别为(591.26±110.30)μg.h.m l-1和(520.20±107.31)μg.h.m l-1;T1/2分别为(18.03±2.36)h和(17.86±2.79)h,以AUC0-60 h计算替硝唑试验制剂对参比制剂的的相对生物利用度为114.64%±10.78%。结论本实验分析方法准确灵敏,重复性好,经统计学分析表明替硝唑受试制...     

单剂量口服非洛地平缓释片的药动学及生物等效性

目的研究单剂量口服国产非洛地平缓释片在健康志愿者体内的药动学特征,并评估其与参比制剂之间的生物等效性。方法 20名健康男性志愿者采用两制剂双周期交叉试验设计。以尼莫地平为内标,采用LC-MS/MS法测定血中药物浓度。以BAPP 2.2计算其药动学参数,评价受试制剂与参比制剂之间的生物等效性。结果 20名受试者单剂量口服10 mg受试制剂和参比制剂后非洛地平的主要药动学参数ρmax）分别为（3.09±1.03）μg·L^-1和（2.68±0.88）μg·L^-1;tmax分别为（3.8±1.0）h和（3.5±1.4）h;t1/2分别为（14.49±2.72）h和（13.74±3.42）h;MRT为（19.87±2.62）h和（19.08±4.73）h;AUC0→48为（30.83±6.04）μg·h·L^-1和（31.42±5.78）μg·h·L^-1;AUG0→∞为（34.00±5.76）μg·h·L^-1和（34.93±6.54）μg·h·L^-1。受试制剂与参比制剂的主要药动学参数经统计学分析无明显差异。受试制剂的相对生物利用度为（98.5±11.0）%。结论国产非洛地平缓释片与其参比制剂之间具有生物等效性。     

伊曲康唑胶囊的人体生物等效性研究

目的 研究两种伊曲康唑胶囊在健康人体的生物等效性.方法 18例健康受试者采用双周期交叉试验,单剂量口服200 mg受试制剂和200 mg参比制剂后,用HPLC法测定血清中伊曲康唑的浓度.计算主要药动学参数,并对两种制剂进行生物等效性评价.结果 受试制剂和参比制剂的主要药动学参数:t1/2分别为22.4±4.4、23.3±4.2 h;Cmax为318.50±106.97、328.15±98.20μg·L-1;Tmax为3.00±0.50、3.30±0.80 h;AUCo-t为4.700±1.766、5.191±1.456 mg·h·L-1;AUCo-∞为5.271±2.139、5.840±1.579 mg.h·L-1.受试制剂的相对生物利用度为89.3%±16.2%.结论 两种制剂生物等效.     

环孢素微乳化口服液健康人体生物等效性研究

目的：研究两种环孢素微乳化口服溶液在健康人体内的药动学及生物等效性。方法：20名健康男性志愿者按自身交叉对照设计,单剂量口服环孢素微乳化口服溶液供试制剂和参比制剂各500 mg。采用HPLC法测定不同时间点全血中环孢素的药物浓度,用DAS软件处理数据,计算主要药动学参数和相对生物利用度,评价其生物等效性。结果：供试制剂和参比制剂的cmax分别为（2.48±0.44）、（2.58±0.43）μg/mL;tmax分别为（1.80±0.60）、（2.00±0.80）h,t1/2分别为（5.04±1.20）、（5.89±1.31）h;AUC0~24 h分别为（15.48±2.42）、（15.24±2.50）μg.h.mL-1;AUC0~∞分别为（16.10±2.70）、（16.09±2.68）μg.h.mL-1;F0~24 h、F0~∞分别为（102.9±15.7）%、（101.6±18.0）%。结论：两制剂具有生物等效性。     

复方苯磺酸氨氯地平/盐酸贝那普利片在健康志愿者的生物等效性

目的:评价2种复方苯磺酸氨氯地平/盐酸贝那普利制剂生物等效性。方法:20名健康男性志愿者随机交叉单剂量口服复方苯磺酸氨氯地平/盐酸贝那普利受试制剂和参比制剂,采用LC-MS/MS法测定血清中氨氯地平、贝那普利及其代谢产物贝那普利拉浓度,DAS2.0软件计算药动学参数与生物等效性。结果:单剂口服受试和参比制剂后的苯磺酸氨氯地平主要药动学参数Cmax分别为(6.6±1.9)μg.L-1和(7.5±2.3)μg.L-1,tmax分别为(6.2±1.4)h和(5.7±1.2)h,AUC0-t分别为(264.2±90.5)μg.h.L-1和(271.3±94.9)μg.h.L-1,受试制剂的苯磺酸氨氯地平相对生物利用度为(97.41±6.04)%;单剂口服受试和参比制剂后的贝那普利主要药动学参数Cmax分别为(136.6±66.1)μg.L-1和(143.3±50.9)μg.L-1,tmax分别为(0.6±0.2)h和(0.6±0.2)h,AUC0-t分别为(139.3±54.0)μg.h.L-1和(137.8±47.2)μg.h.L-1,受试制剂的贝那普利相对生物利用度为(100.8±7.55)%;单剂口服受试和参比...     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

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.