头孢羟氨苄赖氨酸盐在家兔体内的药代动力学研究

采用微生物法测定家兔血浆中的活性成分研究头孢羟氨苄赖氨酸盐的药代动力学.实验结果表明,静脉注射羟氨苄头孢菌素在家兔体内的药代动力学符合三室开放模型,其数学表达式分别为C=620.3e~(-26.02)t+78.3e~(-2.07)t+3.91e~(0.224)t.主要药代动力学参数:三相半衰期为t_(1/2)α=0.027±0.014小时,t_(1/2)β=0.34±0.1小时,t_(1/2)γ=0.09±0.65小时;消除速度常数:K_(10)=8.87±3.3小时~(-1);总表观分布容积Vd=7.22±2.9L.     

双抗体夹心-酶联免疫吸附法测定家兔血清中短尾蝮蛇毒磷脂结合抗凝蛋白的浓度及其药动学研究

目的:建立测定家兔血清中短尾蝮蛇毒磷脂结合抗凝蛋白(PBAP)浓度的方法,并考察其药动学特征。方法:取家兔随机分为低、高剂量组(短尾蝮蛇毒PBAP,0.4、0.8mg·kg-1)和阴性对照组(生理盐水),每组5只,耳缘静脉单次给予相应药物,给药前及给药后1、5、15、30、60、120、240、480min分别从颈总动脉取血,加入到短尾蝮蛇毒PBAP抗体包被酶标板(浓度为100μg·mL-1)中,以给药前的正常血清作为空白对照,用双抗体夹心-酶联免疫吸附(ELISA)法测定不同时间点血清中短尾蝮蛇毒PBAP的浓度,并用DAS2.0软件计算其药动学参数。结果:短尾蝮蛇毒PBAP检测浓度的线性范围为0.0024～10μg·mL-(1r=0.9703),平均回收率为98.78%,平均板内变异系数为7.96%,平均板间变异系数为10.94%;低、高剂量短尾蝮蛇毒PBAP的主要药动学参数分别为t1/2α(9.553±4.668)、(9.873±1.433)min,t1/2β(201.295±66.060)、(205.798±76.834)min,cmax(0.685±0.160)、(2.333±0.478)mg·L-1,AUC0～∞(27.114±2.781)、(61.625±11.631)mg·min·L-1。结论:ELISA法准确、灵敏、特异性强,可用于短尾蝮蛇毒PBAP在家兔血清中的药动学研究。     

倍半氧化羧乙基锗在兔体中药代动力学

本文应用本基荧光酮分光光度法测定倍半氧化羧乙基锗在兔体内的药代动力学,家兔灌胃给药600mg/kg,其经时变化按双室模型处理,结果表明:灌胃给药吸收较快Ka为1.729±0.8390h~(-1),t1/2为4.4±1.7h,tmax 1.6±0.42h.静注给药消除速率较灌胃快,K为0.5489±0.0616h~(-1),t1/2β1.27±0.147h,C1_B为293.7±31.1ml/kgh。     

苯乙烯皮肤染毒在家兔体内的毒物动力学

<正> 家兔在体皮肤苯乙烯(styrene)545.4mg/kg染毒,染毒面积150cm~2,约占家兔体表面积的12％,染毒密度6.98±0.44mg/cm~2,室温25±0.5℃,相对湿度56±5％,风速0.02M/s,家兔皮肤表面温度38.1±0.22℃。用气相色谱法测定血中苯乙烯浓度,并计算毒代动力学参数。其特征如下:1.经皮肤吸收快,Kα=0.7020±0.5268min~(-1),t_(1/2)kα=1.39±0.75min,约6.24min吸收相基本结束。2.吸收程度低,C_(max)=     

离子对液相色谱法测定人血浆中替米沙坦的浓度及药动学研究

目的建立测定人血浆中替米沙坦浓度的高效液相色谱方法,并用该法研究替米沙坦片在健康人体内的药动学。方法色谱柱为Sh im-pack VP-ODS(150mm×4.6mm),流动相为乙腈-0.05%戊磺酸钠-0.05 mol.L-1磷酸二氢钾(50∶25∶25),荧光检测,激发波长为305nm,发射波长为365nm。结果血浆样品在3.05~610.0μg.L-1内线性相关(r=0.9999,n=5)。平均绝对回收率为85.1%(RSD=1.63%),相对回收率大于95.0%,日间和日内相对标准差小于10.0%。10名男性健康志愿者单次口服80mg替米沙坦片后,其药代动力学参数分别为:t1/2(19.8±5.66)h,cm ax(310.7±91.6)μg.L-1,tm ax(1.01±0.40)h。结论此方法准确,灵敏,适于体内药物分析;药动学参数为临床合理用药提供理论依据。     

高效液相色谱法测定左旋西替利嗪血药浓度及其药动学

目的建立HPLC法测定人血浆中左旋西替利嗪浓度,用于左旋西替利嗪人体药动学研究.方法18名健康志愿者口服左旋西替利嗪胶囊后,分别于0,0.25,0.5,0.75,1.0,1.5,2.5,4,8,12,24,36,48 h抽取肘部静脉血各4～5 mL,用HPLC法检测血浆中左旋西替利嗪浓度,并计算药动学参数.HPLC条件是以NucleodurC18柱(250 mm×4.6 mm,5 μm)为分离柱,流动相为乙腈0.05 mol·L-1磷酸二氢胺(4654,v/v),非那吡啶为内标,UV检测波长为254 nm和410 nm.结果主要药动学参数t1/2α,t1/2β,Cmax,tmax,Vd,AUC0-48,AUC0-∞分别为(1.4±0.9)h,(8.4±2.4)h,(0.35±0.11)mg·L-1,(1.18±0.27)h,(0.41±0.06)L·kg-1,(3.6±0.8)mg·h·L-1,(4.1±0.9)mg·h·L-1.血浆中左旋西替利嗪在0.013～0.800 mg·L-1浓度范围内线性良好(r=0.999 7),高中低浓度的平均回收率为80.78%～92.08%,日内RSD和日间RSD均小于15%.结论左旋西替利嗪在正常人体内的分布呈二室开放模型,主要药动学参数与国外文献报道一致,所建立的方法简便、快速、准确,适用于药动学研究.     

HPLC法测定人血浆中舒必利浓度及其人体药动学和相对生物利用度研究

目的:建立HPLC法测定人血浆中舒必利浓度,并研究其药动学及相对生物利用度。方法:采用固相萃取HPLC法,以甲氧氯普胺为内标,乙腈∶5 mmol/L磷酸二氢钾溶液(45∶55,V/V)为流动相,检测波长:λex 244 nm,λem 280 nm。18名受试者随机分成两组,采用双周期交叉试验设计,以HPLC法测定血药浓度,计算药动学参数并进行方差分析,以双单侧t检验进行生物等效性判定。结果:舒必利血浆浓度在6.76~1 689.6 ng/mL范围内样品浓度与峰面积比之间线性关系良好,回归方程为Y=0.00289079X+0.00247349(r=0.9998,n=9),方法回收率90%~110%,日内日间RSD<5%。18名男性健康志愿者单剂量口服100 mg受试制剂或参比制剂后AUC0→36分别为(3 996.0±579.5)ng.h.mL-1和(3 939.6±469.7)ng.h.mL-1,AUC0→∞分别为(4 715.5±753.2)ng.h.mL-1和(4 629.7±773.2)ng.h.mL-1,Tmax分别为(3.3±0.8)h和(2.7±1.0)h,Cmax分别为(362.9±118.7)ng.mL-1和(358.9±98.9)ng.mL-1,t1/2分别为(10.3±3.8)h和(9.7±4.1)h。受试制剂对参比制剂的相对生物利用度为101.9%±13.7%。结论:HPLC法能快速、准确的测定人血浆中的舒必利浓度;受试制剂与参比制剂具有生物等效性。     

紫杉醇纳米脂质体在大鼠体内的药动学

目的对紫杉醇纳米脂质体在大鼠体内的药动学进行研究.方法大鼠尾静脉注射紫杉醇纳米脂质体及紫杉醇注射液,建立液相-质谱联用分析(LC-MS/MS)方法测定血浆中的紫杉醇药物浓度.结果血药浓度在0.2～1 000 μg·L-1范围内线性良好(r=0.999 6),方法回收率及提取回收率均大于90%,日内,日间精密度RSD＜15%.紫杉醇纳米脂质体及市售紫杉醇注射液血浓经时曲线均符合二室模型.t1/2α分别为(0.71±0.25)h和(0.438±0.023)h,t1/2β分别为(13.2±1.2)h和(7.8±1.4)h,AUC分别为(4 519.7±791.3)μg·L-1·h和(2 679.2±530.7 μg·L-1·h).结论本法灵敏度高,准确、可靠.与市售紫杉醇注射液相比,紫杉醇纳米脂质体有一定的长循环作用且可提高在大鼠体内的生物利用度.     

HPLC-荧光法测定莫西沙星在犬体内的血药浓度及其药动学研究

目的:建立测定犬血浆中莫西沙星浓度的方法,并研究其药动学特性。方法:取Beagle犬6只,单剂量灌服莫西沙星120mg,采用高效液相色谱-荧光法测定给药后72 h内血浆中莫西沙星的浓度,采用DAS软件计算药动学参数。色谱柱为HypersilBDS C18,流动相为乙腈-1.0 mol.L-1醋酸溶液(25∶75,pH=2.0),流速为1.0 mL.min-1,激发波长为273 nm,发射波长为488 nm。结果:莫西沙星检测浓度的线性范围为0.1～20.0μg.mL-(1r=0.999 2),平均相对回收率为89.5%～96.7%,日内和日间RSD均<6%。莫西沙星在犬体内的药动学特性符合二室模型,主要药动学参数cmax:(10.25±4.21)μg.mL-1,tmax:(3.0±1.0)h,t1/2β:(9.76±2.48)h,AUC0～24 h:(142.10±49.80)mg.h.L-1。结论:本方法准确、灵敏、快速,适用于莫西沙星的血药浓度测定和药动学研究。     

RP-HPLC法测定家兔血浆中甲苯喹哌浓度和药代动力学参数

本文建立了以紫外230nm波长检测的反相高效液相色谱法(RP-HPLC)测定家兔血浆中甲苯喹派浓度。填料使用LiChrosorb RP-C18,流动相为甲醇—水—三乙胺—磷酸(63:37:1:0.8 v/v),血样(或尿样)经碱化后用乙醚提取,再以0.2 mol/L硫酸回提,进样。方法回收率为99.84±3.10(SD)%;天内、天间精密度平均CV为4.12%及3.95%(n=5);最低检测限3ng.经提取的标准线性浓度在25～2000 ng/ml范围内,Y=0.002865X-0.01346,r=0.9999,内源性物质及可能的合并用药不干扰色谱测定。文内用质谱法鉴定血样中甲苯喹哌色谱峰纯度,并由尿样分析对其主要代谢物予以初步验证。本法可应用于药代动力学参数测定。家兔按8mg/kg静注后,药—时曲线符合二室模型T_1/2=4.8008±1.1522(SD)h。     

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.     

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.