酒石酸唑吡坦片在汉族健康人体内的药动学研究

目的:研究酒石酸唑吡坦片在汉族健康人体内的药动学。方法:10名汉族健康受试者口服酒石酸唑吡坦片10mg后,用高效液相色谱-荧光检测法测定血浆中唑吡坦的浓度,用DAS2.0.1程序计算药动学参数。结果:汉族健康受试者口服酒石酸唑吡坦片后,药-时曲线符合一级吸收一室模型,主要药动学参数分别为tma(x0.9±0.5)h、Cma(x190.8±70.6)μg·L-1、t1/(22.2±0.6)h、Vd/F(0.938±0.256)L·kg-1、CL/F(18.09±10.22)L·h-1、AUC0～1(2624.9±190.8)μg·h·L-1、AUC0～∞(650.1±208.4)μg·h·L-1。结论:健康受试者单剂量口服酒石酸唑吡坦片的药动学参数与文献报道基本一致,可作为不同民族人群药动学研究的基础。     

酒石酸唑吡坦片在蒙古族和汉族人体内的药动学研究

目的:研究酒石酸唑吡坦在我国蒙古族和汉族健康受试者体内的药动学。方法:选择蒙古族和汉族健康受试者各10名(男、女各5名),分别口服酒石酸唑吡坦10mg后,用高效液相色谱-荧光检测法测定受试者血浆中酒石酸唑吡坦的浓度,以DASVer2.0计算药动学参数,研究其药动学过程。结果:蒙、汉两民族受试者口服酒石酸唑吡坦后,药-时曲线均符合一室开放模型,主要药动学参数分别为t1/(22.47±0.50)、(2.21±0.77)h,tma(x0.90±0.38)、(0.93±0.47)h,Cma(x221.85±109.97)、(190.81±70.59)μg·L-1,AUC0～1(2770.00±405.64)、(624.48±192.15)μg·h·L-1,AUC0～∞(808.85±434.10)、(649.58±210.17)μg·h·L-1。结论:本方法可用于人体内酒石酸唑吡坦的的药动学研究,两民族受试者各主要药动学参数之间无显著性差异。     

酒石酸唑吡坦口溶片的药动学及生物等效性研究

目的:研究酒石酸唑吡坦口溶片的药动学及生物等效性。方法:采用随机自身对照双周期交叉试验设计,18名健康受试者单剂量口服受试制剂7.5mg或参比制剂10mg后,用高效液相色谱-荧光法测定人血浆中的唑吡坦浓度,用非房室模型法估算唑吡坦的药动学参数。结果:受试制剂与参比制剂的主要药动学参数分别为:Cmax(117.62±24.39)、(126.30±35.27)μg·L-1,tmax(0.69±0.16)、(1.25±0.29)h,AUC0～τ(431.16±109.25)、(451.58±114.25)μg·h·L-1,AUC0～∞(450.79±108.03)、(465.34±121.89)μg·h·L-1。受试制剂相对于参比制剂的生物利用度为(97.9±10.7)%。结论:2种国产唑吡坦片剂吸收程度等效而吸收速度不等效。     

国产酒石酸唑吡坦片剂人体生物等效性研究

目的:研究国产酒石酸唑吡坦片剂和进口酒石酸唑吡坦片剂的人体生物等效性。方法:采用高效液相荧光检测法,测定18例男性健康受试者单剂量口服10 mg国产和进口酒石酸唑吡坦片剂的唑吡坦血浆浓度。采用3p97程序对主要的药动学参数Cmax,AUC0-12h,Tmax进行统计分析。结果:国产和进口酒石酸唑吡坦片剂的Cmax、分别为(113．73±11．40)和(116．58±16．13)ng·mL-1,Tmax分别为(1．01±0．25)和(1．03±0．24)h,t1/2 ke分别为(3．02±0．29)和(2．92±0．42)h,AUC0-12 h分别为(413．81±61．64)和(434．0±62．20)ng·h·mL-1。2种制剂的Cmax,AUC0-12h和Tmax无显著性差异。国产酒石酸唑吡坦片剂相对生物利用度为(95．50±7．50)％。结论:国产和进口酒石酸唑吡坦片剂两种制剂具有生物等效性。     

高效液相色谱法测定人血浆中酒石酸唑吡坦的浓度

目的:建立HPLC法测定人血浆中酒石酸唑吡坦浓度。方法:采用Hypersil C_(18)色谱柱(200 mm×4.6 mm,5μm);流动相:0.02 mol·L~(-1)磷酸二氢钾(含0.5%三乙胺,pH=4.0)-甲醇(38:62);流速:1.2 ml·min~(-1);柱温:30℃;激发波长:300 nm,发射波长:385 nm。结果:血浆酒石酸唑吡坦在2～200 ng·ml~(-1)浓度范围内线性关系良好(r=0.999 9)。低、中、高3种浓度相对回收率分别为102.0%,102.1%,98.9%,日内、日间RSD均小于10%。结论:本法可用于血浆中酒石酸唑吡坦浓度的测定。     

UHPLC法测定辐射后的酒石酸唑吡坦片含量

目的建立UHPLC法测定辐射后的酒石酸唑吡坦片含量,考察不同辐射剂量对酒石酸唑吡坦片含量的影响。方法采用超高效液相色谱法,对γ射线辐射的酒石酸唑吡坦片进行含量测定。采用C₁₈柱以乙腈-甲醇-0.05 mol/L磷酸溶液(用三乙胺调节pH值至5.5)(18∶26∶56)为流动相,流速为0.7 ml/min,检测波长为254 nm。结果酒石酸唑吡坦浓度在5～80μg/ml范围内线性良好,r=0.999 6;平均加样回收率为98.2%,RSD为1.72%,重复性为0.87%。0、8、25和80 kGy辐射量下酒石酸唑吡坦含量分别为105.1%、106.4%、102.7%和105.4%。结论超高效液相色谱法分析周期短、结果准确,适用于辐射后酒石酸唑吡坦片的含量测定,辐射后酒石酸唑吡坦片含量基本保持不变。     

国产酒石酸唑吡坦的生物利用度和生物等效性研究

目的:研究国产酒石酸唑吡坦在中国健康受试者体内的生物利用度和生物等效性.方法:采用高效液相色谱法测定18例健康受试者单剂量口服受试制剂或参比制剂10 mg后血浆中唑吡坦的浓度,采用BAPP2.0生物统计软件对2种制剂的Cmax,Tmax和AUC0-t进行统计分析.结果:酒石酸唑吡坦受试制剂与参比制剂的实测Tmax均为(0.9±0.3)h,实测Cmax分别为(173.94±57.49)和(173.74±47.99)μg·L-1, 梯形法计算AUC0-t分别为(543.19±252.06)和(551.01±254.65)μg·h·L-1,t1/2Ke分别为(2.22±0.61)和(2.12±0.40)h.2种制剂的主要药动学参数经统计分析差异无显著性.酒石酸唑吡坦受试片剂的相对生物利用度为(99.9±20.7)%.结论:受试制剂和参比制剂具有生物等效性.     

单剂量口服酒石酸唑吡坦在中国朝鲜族和汉族健康人体内的药代动力学

目的 研究酒石酸唑吡坦(镇静催眠药)在中国朝鲜族和汉族健康受试者体内的药代动力学.方法 选择朝鲜族和汉族健康受试者各10名(5男、5女),每人口服酒石酸唑吡坦10 mg后,用高效液相色谱-荧光检测法测定受试者血浆中酒石酸唑吡坦的血药浓度,用DAS 2.0药代动力学软件进行数据处理.结果 朝鲜、汉两民族受试者口服酒石酸唑吡坦后主要药代动力学参数,t1/2分别为(2.04±0.47),(2.21±0.77) h,tmax分别为(0.98±0.22),(0.93±0.47)h,Cmas分别为(178.13±43.08),(190.81±70.59) μg·L-1,AUC0-12分别为(578.88±216.25),(624.48±192.15) μg·L-1·h,AUC0-∞分别为(597.48±227.97),(649.58±210.17) μg·L发-1·h.结论 服用酒石酸唑吡坦后,汉族,朝鲜族受试者各主要药代动力学参数之间无显著差异(P>0.05).     

反相高效液相色谱法测定兰索拉唑及其代谢产物5''-羟基兰索拉唑和兰索拉唑砜的血药浓度

目的 :建立测定兰索拉唑及其代谢产物 5’ 羟基兰索拉唑和兰索拉唑砜的血药浓度的方法 ,用于测定其血药浓度并进行临床药代动力学研究。方法 :采用高效液相 二极管阵列色谱法测定兰索拉唑及其代谢产物 5’ 羟基兰索拉唑和兰索拉唑砜的血药浓度。结果 :兰索拉唑的校正标准曲线为Y =0 .0 135 8+0 .0 0 12 2 7X (r =0 .9994 ) ,其 2 5 ,2 0 0 ,2 0 0 0μg·L-1三浓度的血样回收率分别为 87.99% ,94 .38% ,77.2 1% ;精密度分别 7.79% ,1.2 1% ,5 .4 9% ;5’ 羟基兰索拉唑的校正标准曲线分别为Y=0 .0 0 2 5 36+0 .0 0 0 912 6X (r=0 .9990 ) ,其 2 0 ,10 0 ,5 0 0 μg·L-1三浓度的血样回收率分别为 85 .85 % ,87.64% ,10 7.70 % ;精密度分别为 10 .73% ,6.98% ,5 .62 % ;兰索拉唑砜的校正标准曲线分别为Y =0 .0 1486+0 .0 0 1462X (r =0 .9995 ) ,其 2 0 ,10 0 ,10 0 0μg·L-1三浓度的血样回收率分别为 79.84 % ,85 .18% ,10 0 .68% ;精密度分别为 9.2 2 % ,2 .36% ,4 .81%。志愿受试者禁食口服 30mg兰索拉唑胶囊后 ,兰索拉唑及其代谢产物 5’ 羟基兰索拉唑和兰索拉唑砜的Cmax 分别为 113.2 1,15 61.5 4 ,131.14μg·L-1。结论 :此方法可满足测定要求 ,可用于兰索拉唑的药代动力学研究。     

高效毛细管电泳法测定复方磺胺甲噁唑片中磺胺甲噁唑和甲氧苄啶的含量

目的　测定复方磺胺甲 口 恶 唑片中磺胺甲 口 恶 唑及甲氧苄啶的含量。方法　采用高效毛细管电泳法 ,肉桂酸为内标 ,运行缓冲液为 2 5mmol·L-1硼砂 硼酸缓冲液 (pH9.2 ) ,内含 3 0mmol·L-1十二烷基磺酸钠及 10 %乙腈 ;运行电压 2 0kV ;检测波长2 14nm。结果　磺胺甲口 恶 唑和甲氧苄啶线性范围分别为 5 0～ 2 5 0 μg/mL(r =0 .9997)和 10～ 5 0 μg/mL(r =0 .9986) ,平均回收率分别为 99.0 %和 98.6% ,RSD分别为 2 .0 %及 2 .6% (n =6)。结论　该方法简便、准确、灵敏 ,适用于复方磺胺甲 口 恶 唑片的质量控制     

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.     

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.     

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.     

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.     

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.