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。     

2种阿奇霉素分散片生物等效性研究

目的:研究2种阿奇霉素分散片的生物等效性。方法:20名男性健康志愿者随机交叉口服阿奇霉素分散片受试制剂或参比制剂500mg,用微生物琼脂平板扩散法测定血药浓度。采用3p97程序计算主要药动学参数及相对生物利用度,以评价生物等效性。结果:受试制剂与参比制剂的药-时曲线基本一致,Cmax分别为(407.672±36.025)、(413.903±36.945)ng.mL-1,tmax分别为(1.950±0.510)、(1.850±0.366)h,t1/2分别为(50.757±18.919)、(48.926±16.402)h,AUC0～120分别为(4998.110±721.271)、(4853.564±539.555)ng.h.mL-1,AUC0～∞分别为(5793.932±700.138)、(5570.704±614.011)ng.h.mL-1。阿奇霉素受试制剂的相对生物利用度为(99.0±17.6)%。结论:2种制剂具有生物等效性。     

马来酸替加色罗分散片的人体生物等效性研究

目的:研究马来酸替加色罗分散片的人体生物等效性。方法:22名健康男性志愿者随机交叉单剂量口服马来酸替加色罗分散片(受试制剂)和马来酸替加色罗片(参比制剂)6mg,采用LC/MS/MS法测定人血浆中药物浓度。结果:受试制剂和参比制剂的tmax分别为(0.86±0.22)、(1.01±0.24)h,Cmax分别为(2.21±0.69)、(2.05±0.64)ng.mL-1,AUC0~17分别为(6.35±2.48)和(6.47±1.99)ng.h.mL-1,AUC0~∞分别为(6.69±2.59)、(6.70±2.03)ng.h.mL-1。受试制剂相对于参比制剂的生物利用度为(98.2±22.1)%。结论:两种制剂具有生物等效性。     

阿莫西林/双氯西林钠分散片的人体生物等效性研究

目的:研究阿莫西林/双氯西林钠分散片的人体生物等效性。方法:采用双周期交叉设计试验,20名健康男性受试者随机交叉单剂量口服阿莫西林/双氯西林钠分散片(受试制剂)和阿莫西林/双氯西林钠胶囊(参比制剂)750mg,以高效液相色谱法测定人血浆中阿莫西林、双氯西林经-时血药浓度,用DAS软件拟合计算药动学参数。结果:受试制剂与参比制剂阿莫西林的tm ax分别为(1.16±0.26)、(1.24±0.27)h,Cm ax分别为(6.32±2.56)、(6.59±2.33)μg.mL-1,AUC0~7分别为(12.27±2.25)、(12.66±2.68)μg.h.mL-1,AUC0~∞分别为(15.48±2.38)、(15.47±3.71)μg.h.mL-1;双氯西林的tm ax分别为(0.94±0.23)、(0.93±0.18)h,Cm ax分别为(12.12±5.71)、(12.12±4.15)μg.mL-1,AUC0~7分别为(23.49±4.20)、(23.25±3.64)μg.h.mL-1,AUC0~∞分别为(24.93±3.96)、(24.50±3.66)μg.h.mL-1。受试制剂阿莫西林与双氯西林的相对生物利用度分别为(97.7±8.2)%、(102.0±16.8)%。结论:阿莫西林/双氯西林钠分散片与阿莫西林/双氯西林钠胶囊具有生物等效性。     

盐酸胺碘酮分散片人体生物等效性研究

目的:研究盐酸胺碘酮分散片的人体生物等效性。方法:采用双周期交叉试验设计,18名健康男性受试者随机交叉单剂量口服盐酸胺碘酮分散片(受试制剂)与盐酸胺碘酮片(参比制剂)400mg,采用液-质联用(LC-MS)法测定人血浆中盐酸胺碘酮经-时血药浓度,利用SPSS10.0统计软件计算药动学参数,评价二制剂的生物等效性。结果:受试制剂与参比制剂的tmax分别为(4.2±1.2)、(3.8±0.9)h,Cmax分别为(420.0±211.7)、(414.8±166.7)ng.mL-1,t1/2分别为(38.8±20.4)、(39.6±12.5)h,AUC0～96分别为(6 375.3±3 093.1)、(6 518.4±3 101.1)ng.h.mL-1,AUC0～∞分别为(7 165.3±3 680.2)、(7 325.5±3478.1)ng.h.mL-1。受试制剂中盐酸胺碘酮的相对生物利用度为(98.4±8.4)%。结论:盐酸胺碘酮分散片与盐酸胺碘酮片具有生物等效性。     

氯沙坦钾片人体生物等效性研究

目的:研究2种氯沙坦钾片的人体生物等效性。方法:20名健康受试者按随机双交叉设计,单剂量口服氯沙坦钾片受试制剂与参比制剂100mg后,采用液-质联用(LC-MS)法测定氯沙坦及其代谢物EXP3174的血药浓度,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氯沙坦的药动学参数分别为Cma(x534.230±238.642)、(520.020±226.800)ng.mL-1,tmax(1.401±0.946)、(1.334±0.750)h,AUC0～36(871.177±232.315)、(773.030±252.209)ng.h.mL-1,AUC0～∞(881.005±235.070)、(781.131±252.455)ng.h.mL-1;其代谢物EXP3174的药动学参数分别为Cma(x1294.000±387.815)、(1140.900±317.615)ng.mL-1,tma(x2.667±1.144)、(2.734±1.162)h,AUC0～36(6267.905±1350.300)、(5719.411±1127.725)ng.h.mL-1,AUC0～∞(6316.605±1343.048)、(5755.335±1138.358)ng.h.mL-1。受试制剂相对生物利用度为(116.6±24.3)%。结论:氯沙坦钾片受试制剂与参比制剂生物等效。     

2种盐酸左氧氟沙星胶囊的人体生物等效性研究

目的:研究2种盐酸左氧氟沙星胶囊的人体生物等效性。方法:22名健康男性志愿者,采用单剂量、随机、自身交叉对照试验设计,分别空腹口服盐酸左氧氟沙星胶囊受试制剂和参比制剂各200mg后,用反相高效液相色谱-荧光检测法检测血清中左氧氟沙星经-时过程的血药浓度,计算其药动学参数和相对生物利用度。结果:受试制剂与参比制剂的Cm ax分别为(2 840.7±371.6)、(2 810.5±440.0)ng.mL-1,t1/2β分别为(7.26±1.21)、(7.28±1.58)h,tm ax分别为(1.13±0.44)、(1.09±0.34)h,AUC0~24分别为(20 908.9±3 178.2)、(20 398.0±2 576.4)ng.h.mL-1,AUC0~∞分别为(23 173.6±3 600.4)、(22 492.4±2 649.0)ng.h.mL-1。受试制剂的相对生物利用度为(103.1±14.1)%。结论:2种盐酸左氧氟沙星胶囊具有生物等效性。     

依诺沙星胶囊在健康人体的相对生物利用度与生物等效性

目的　建立测定血浆依诺沙星浓度的HPLC-UV法并研究依诺沙星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, 20名男性健康志愿者分别单剂量口服2种国产依诺沙星胶囊(参比制剂)和(受试制剂),用HPLC法测定血药浓度,计算药代动力学参数,并评价2制剂的生物等效性。结果　口服依诺沙星胶囊参比制剂及受试制剂400mg后的主要药代动力学参数:Cmax分别为(2. 98±0. 65)和(2. 90±0. 63)mg·L-1;tmax分别为(1. 23±0. 47)和(1. 43±0. 47)h;AUC(0→24)分别为(18. 20±4. 60)和(19. 71±4. 31)mg·h·L-1;t1 /2Ke分别为(6. 08±1. 23)和(5. 88±0. 89)h。受试制剂对参比制剂平均相对生物利用度F0→24为( 112. 0±26. 7 )%,F0-inf为(112. 2±28. 1)%。结论　2种依诺沙星胶囊制剂生物等效。     

2种阿莫西林分散片人体药动学及生物等效性研究

目的:研究2种阿莫西林分散片在人体内的药动学及生物等效性。方法:采用随机自身交叉对照试验设计,20名健康男性志愿者分别单剂量口服500mg阿莫西林受试制剂与参比制剂后,采用高效液相色谱法测定血浆阿莫西林的浓度,用DAS药动学软件计算二者药动学参数及生物利用度。结果:阿莫西林受试制剂与参比制剂的药动学参数分别为:Cma(x11.11±3.63)、(9.93±3.39)μg.mL-1,tma(x1.14±0.42)、(1.34±0.47)h,t1/(21.08±0.52)、(1.07±0.66)h,AUC0～(624.49±6.22)、(22.44±5.98)μg.h.mL-1,AUC0～∞(25.21±6.44)、(23.40±6.25)μg.h.mL-1。以AUC0～6估算,受试制剂相对于参比制剂的生物利用度为110.3%。结论:2种阿莫西林分散片生物等效,可以替换使用。     

3种司帕沙星制剂在健康人体内的药动学及生物等效性研究

目的:比较3种司帕沙星制剂在健康人体内的药动学,并评价3种制剂的生物等效性。方法:24名健康受试者,单剂量三交叉分别口服司帕沙星胶囊(受试制剂1)、司帕沙星片(受试制剂2)和司帕沙星胶囊(参比制剂)400mg后,用高效液相色谱法测定受试者血浆中司帕沙星的血药浓度,用DAS2.1.1软件计算药动学参数,并评价生物等效性。结果:受试者口服司帕沙星受试制剂1、2和参比制剂后的主要药动学参数分别为:cmax(1.614±0.572)、(1.760±0.498)、(1.609±0.419)μg·mL-1,tmax(4.563±2.188)、(4.708±2.116)、(4.542±2.226)h,t1/2(21.890±5.150)、(21.954±6.808)、(23.336±5.762)h,AUC0～72h(42.809±12.684)、(44.559±10.787)、(43.193±8.757)μg·h·mL-1,AUC0～∞(48.149±14.678)、(50.697±14.812)、(49.588±11.484)μg·h·mL-1。受试制剂1、2的F0～72h分别为(104.2±25.9)%、(96.9±20.7)%。统计分析表明,2种司帕沙星受试制剂的cmax、tmax、AUC0～72h、AUC0～∞与参比制剂相比均无显著性差异。结论:3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.