头孢丙烯在下呼吸道细菌感染患者的药代动力学研究

目的通过研究下呼吸道细菌感染患者的头孢丙烯临床药代动力学参数,为临床选择合理给药方案提供依据。方法用HPLC法测定10例下呼吸道细菌感染患者连续给药5 d后的稳态血药浓度,数据用3P 97药物动力学模拟系统处理。结果头孢丙烯的药-时曲线符合二室开放模型,主要药代动力学参数;t1/2为1.55±0.17h,M RT为2.52±0.15h,Cm ax为13.32±1.28μg.mL-1,tm ax为1.41±0.31h,AUC0~10为31.68±7.68μg/(h.mL-1)。结论口服头孢丙烯片500m g,每天2次,能获得控制下呼吸道细菌感染的有效治疗浓度。     

乳酸司氟沙星片人体生物等效性研究

目的 :研究乳酸司氟沙星片在健康人体内的药代动力学与相对生物利用度 ,以评价其生物等效性。方法 :采用高效液相色谱法测定10名健康志愿者随机交叉口服单剂量 (400mg)乳酸司氟沙星片与参比制剂 (司帕沙星片 )后血浆中司帕沙星的药 -时数据 ,经3p97药代动力学程序拟合 ,计算其药代动力学参数并评价其生物等效性。结果 :乳酸司氟沙星片与司帕沙星片的主要药代动力学参数分别为 :T1/2β= (22 05±1 70)h、(22 23±1 77)h ;Cmax = (1 80±0 16) μg/ml、(1 74±0 16) μg/ml ;Tmax = (4 11±0 68)h、(3 96±0 80)h ;AUC0～t= (49 12±4 53)h/ (μg·ml)、(45 82±5 32)h/ (μg/ml)。乳酸司氟沙星片的相对生物利用度为(107 57±8 47) %。结论 :乳酸司氟沙星片与参比制剂司帕沙星片为生物等效制剂     

用HPLC法和微生物法测定人血浆中头孢丙烯浓度的比较

目的:比较用HPLC法和微生物法测定人血浆中头孢丙烯浓度的差异。方法:10名健康志愿者单剂量口服头孢丙烯片500 mg,分别用HPLC法和微生物法测定血浆中药物浓度。结果:HPLC法线性范围为0．143～14．300μg／mL,低、中、高浓度(0．357 5、1．430 0、7．150 0μg／mL)的回收率分别为(101．75±7．71)％、(96．89±2．55)％和(98．70±1．67)％(n= 6);3种浓度的日内、日间RSD分别为7．58％0、2．63％、1．69％和7．11％、3．77％、2．01％(n=6)。微生物法线性范围为0．25～3．00μg／mL,低、中、高浓度(0．50、1．75、3．00μg／mL)的回收率分别为(96．37±5．99)％、(108．26±8．39)％和(105．12±10．35)％(n=5);3种浓度的日内、日间RSD分别为9．84％、7．75％、6．22％和10．05％、8．31％、7．87％(n=5)。结论:两种方法回收率和精密度均符合要求,受试者各时间点平均血药浓度测定值无显著性差异。     

2种头孢克罗胶囊的人体药代动力学及相对生物利用度研究

目的 :研究2种头孢克罗胶囊在健康人体内的药代动力学与相对生物利用度。方法 :采用HPLC法测定人体血浆药物浓度 ,所有受试者随机交叉单剂量口服500mg 国产或进口头孢克罗胶囊。结果 :2种药品的药 -时曲线符合一室开放模型 ,国产和进口头孢克罗胶囊的峰浓度Cmax 为(13 24±2 42)和(13 29±3 14)μg/m1 ;达峰时间Tmax 为(0 58±0 192)和(0 55±0 10)h ;消除半衰期T1/2 为(0 42±0 09)和(0 41±0 09)h ,药 -时曲线下面积AUC0～T 为(15 81±1 53)和(15 68±1 97)h/(μg m1)。结论 :国产与进口头孢克罗胶囊具有生物等效性 ,国产胶囊的相对生物利用度为(100 84±7 78) %。     

LC/MS/MS法测定人血浆中非那雄胺的浓度及其药代动力学研究

目的:建立LC/MS/MS法测定人血浆中非那雄胺的浓度,并研究其在中国男性健康人体内的药代动力学。方法:采用LC/MS/MS(APCI源)测定非那雄胺的血浆浓度,并计算其药代动力学参数。结果:非那雄胺线性范围为0.2～50.0μg·L~(-1),定量下限为0.2μg·L~(-1)。日内、日间精密度(RSD)均小于10%,准确度(PE)在±3％内。应用本法测得18名中国男性健康志愿者口服5mg非那雄胺片后主要药代动力学参数为:t_(1/2ke)为5.57±1.60h,K_e为0.12±0.06H~(-1),t_(max)为2.31±0.82h,C_(max)为4O.31±10.89μg L~(-1);AUC_(0-t)和AUC(0-∞)分别为267.9±75.0μg h L~(-1)和286.6±88.6μghL~(-1)。结论:该法操作简便、快速、灵敏,可用于测定血浆中非那雄胺浓度。     

乌苯美司在犬体内的药动学和绝对生物利用度

建立了RP-HPLC法在258nm测定犬血浆中乌苯美司的浓度,方法定量限为0．625μg／ml,日内、日间差小于5．0％, 平均同收率大于95．0％。采用双周期自身交叉设计,在7条Beagle犬中进行口服及静脉给药的药物动力学研究,清洗期为 8d。Beagle犬静注乌苯美司200mg后的药-时曲线符合三室模型,口服给药的C_(max)为(31．54±5．164)μg/ml,T_(max)为(1．50 ±0．41)h,T_(1/2)为(1．53±0．48)h,AUC_o→t为(92．85±10．74)μg·ml~(1-)·h。平均绝对生物利用度为(67．61±11．75)％。     

阿奇霉素干混悬剂 颗粒剂和胶囊的人体药代动力学研究

目的使用高效液相色谱-质谱(HPLC-MS)联用法测定人血浆中阿奇霉素的浓度,并研究阿奇霉素干混悬剂、颗粒剂和胶囊在健康人体内的药代动力学情况。方法 20名健康男性志愿者单剂量口服500mg阿奇霉素后,采集不同时间点血样测定血药浓度。结果阿奇霉素的线性范围为2.71～1084μg/L,日内和日间相对标准偏差(RSD)均<5.0%。阿奇霉素干混悬剂主要药代动力学参数为:Cmax:(453±130)μg/L;tmax:(2.3±0.9)h;t1/2:(48±6)h;平均驻留时间(MRT):(53±8)h;曲线下面积(AUC)0-t:(4694±903)μg·h-·1L-1;AUC0-∞:(5118±919)μg·h-1·L-1。结论 3种剂型阿奇霉素的药代动力学参数的差异无统计学意义。     

司帕沙星胶囊的药代动力学及相对生物利用度研究

目的研究司帕沙星胶囊的药代动力学和相对生物利用度。方法采用HPLC法测定18名健康男性志愿者,随机自身交叉单剂量口服司帕沙星胶囊300mg后的血药浓度,得出相应的药时曲线,计算各药代参数和相对生物利用度。结果18名健康志愿者单次口服司帕沙星胶囊300mg的主要药代动力学参数分别为:t1/2(23.59±4.54)和(22.90±3.56)h;Cmax(1205.36±390.85)和(1143.01±309.33)μg.L-1;tmax(4.3±1.1)和(4.4±1.0)h;MRT(33.74±6.23)和(32.72±4.52)h;AUC0～96h(33365.80±9661.41)和(31571.94±7733.55)μg.h.L-1;AUC0～∞(35753.55±9909.80)和(33880.92±8113.03)μg.h.L-1。2种制剂的药动学参数无显著性差异(P>0.05),受试制剂的相对生物利用度(F)为(105.10±11.20)%。结论2种制剂具有生物等效性。     

奥美拉唑肠溶胶囊人体药代动力学及生物等效性研究

目的:研究两厂家产奥美拉唑肠溶胶囊在正常人体的药代动力学与生物等效性。方法:将18名健康男性志愿受试者随机交叉口服 40mg奥美拉唑肠溶胶囊受试制剂和参比制剂后,采用高效液相色谱法,以卡马西平为内标,测定奥美拉唑的血浆药物浓度。结果:受试和参比制剂均符合一级吸收开放性一室模型,主要药代动力学参数0-12 h药-时曲线下面积(AUC0→12)分别为(2 719．9±1 551．7),(2 820．8± 1 668．1)ng·h/mL,峰浓度(Cmax)分别为(820．1±420．1),(760．0±415．4)ng/mL,达峰时间(Tmax)分别为(2．4±0．6),(2．5±0．6)h,血浆半衰期(t1/2)分别为(2．2±0．8),(2．4±0．9)h。相对生物利用度为(99．69±13．51)％。结论:两种奥美拉唑肠溶胶囊为生物等效制剂。     

法罗培南钠片在健康人体中的药代动力学研究

目的研究健康志愿者单次口服3个剂量法罗培南钠片的药代动力学。方法 12名健康志愿者,男女各半,随机分为3组,分别口服150、300和600 mg法罗培南钠片后,采用HPLC法测定血浆和尿液中法罗培南的浓度,应用DAS软件计算其药代动力学参数。结果单次口服3个剂量组(150、300和600 mg)法罗培南钠片,血浆中法罗培南的主要药代动力学参数:AUC0～t分别为(3.73±2.77)、(6.72±4.12)和(13.1±8.04)μg.h/mL;Cmax分别为(1.89±0.93)、(3.19±1.14)和(6.95±3.37)μg/mL;Tmax分别为(0.97±0.54)、(0.83±0.38)和(0.93±0.45)h;t1/2分别为(0.92±0.26)、(0.94±0.14)和(0.98±0.15)h。累积尿药排泄率分别为(6.23±7.09)%、(4.69±4.32)%和(4.14±2.95)%。结论健康人口服150～600 mg法罗培南钠片后,法罗培南在体内符合线性药代动力学特征。     

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.