头孢呋辛酯分散片在健康志愿者的药代动力学和相对生物利用度

目的研究口服头孢呋辛酯分散片在18名健康志愿者体内药代动力学和相对生物利用度.方法用双交叉试验,18名健康志愿者口服单剂量头孢呋辛酯分散片和片剂两种制剂0.5g,用RP-HPLC法测定人血浆中头孢呋辛浓度.结果分散片和片剂t1/2分别为(1.80±0.32)和(1.94±0.29)h,tmax分别为(1.4±0.3)和(1.9±0.5)h,Cmax分别为(8.89±1.44)和(8.33±1.24)mg.L-1,AUC0-10分别为(28.56±3.70)和(27.15±3.83)mg.h.     

盐酸氨溴索分散片人体药动学

目的:研究健康人体单剂量口服盐酸氨溴索分散片的药动学。方法:采用双周期交叉自身对照试验方法,18例健康志愿者单剂量口服盐酸氨溴索分散片和普通片各90 mg,采用反相高效液相色谱法测定血浆中盐酸氨溴索浓度,计算并比较两者的主要药动学参数。结果:盐酸氨溴索分散片和普通片在健康志愿者血浆中的Tm ax分别为(1.77±0.39)和(2.02±0.38)h;Cm ax分别为(240.04±98.88)和(247.34±90.13)μg.L-1;t1/2分别为(7.40±1.63)和(7.12±1.56)h;AUC0~36 h分别为(1 556.22±474.00)和(1 633.89±402.03)μg.h.L-1;AUC0~∞分别为(1 607.13±489.33)和(1 690.79±436.43)μg.h.L-1。除Tm ax外,盐酸氨溴索分散片和普通片各主要药动学参数间均无统计学差异(P>0.05)。结论:盐酸氨溴索分散片与普通片相比,具有起效快的特点。     

恶丙嗪分散片在健康人体内的生物利用度及生物等效性研究

目的比较恶丙嗪分散片和普通片剂的生物利用度和生物等效性.方法采用HPLC法测定了20名健康志愿者分别单剂量口服400mg恶丙嗪后,不同时间的血药浓度,并进行生物等效性评价.结果恶丙嗪分散片和普通片的Cmax分别为(62.04±12.44)mg@L-1和(60.52±11.49)mg@L-1,tmax分别为(3.85±0.67)h和(4.05±0.94)h,t1/2分别为(41.63±0.93)h和(41.11±7.72)h,AUC0-96为(1339±220)mg@h@L-1和(1367±247)mg@n@L-1.恶丙嗪分散片的人体相对生物利用度为98.85%±11.88%.结论恶丙嗪分散片与普通片剂具有生物等效性.     

2种盐酸氨溴索制剂的人体药动学研究

目的:比较盐酸氨溴索分散片与盐酸氨溴索普通片在健康人体内的药动学差异。方法:12名男性健康志愿者均分为2组,分别单剂量口服盐酸氨溴索分散片与盐酸氨溴索普通片各90mg,采用高效液相色谱法检测盐酸氨溴索的血药浓度,并用DAS2.1软件进行数据处理。结果:盐酸氨溴索分散片与盐酸氨溴索普通片主要药动学参数分别为:cma(x697.8±78.4)、(564.3±63.9)μg·L-1,tma(x2.9±0.2)、(4.7±0.6)h,t1/(24.8±0.7)、(5.8±0.9)h,AUC0～∞(5795.6±184.7)、(4516.4±114.9)μg·h·L-1,AUC0～24h(4643.8±107.6)、(3717.5±87.6)μg·h·L-1。结论:盐酸氨溴索分散片tmax、t1/2小于普通片,AUC0～t、AUC0～∞、cmax高于普通片,说明盐酸氨溴索分散片具有良好的速释效果。     

克拉霉素分散片的相对生物利用度

目的 :比较国产克拉霉素分散片与进口克拉霉素片 (克拉仙 )的相对生物利用度。方法 :采用微生物法测定8名健康男性志愿者随机单剂量口服两种片剂500mg后 ,药物在体内的经时过程。结果 :药 -时曲线符合一级吸收二室模型 ,国产分散片与进口片AUC分别为 (18 58±5 46) μg/(h·ml)和 (19 05±5 75) μg/(h·ml) ;Cmax 分别为 (2 88±0 74) μg/ml和 (2 74±0 65) μg/ml;Tmax 分别为 (1 28±0 41)h和 (1 47±0 51)h ,分散片的相对生物利用度为 (98 49±16 00) %。结论 :国产克拉霉素分散片与进口克拉霉素普通片生物等效。     

头孢氨苄胶囊在人体药代动力学及其相对生物利用度的研究

目的 :研究头孢氨苄胶囊在人体内的药物动力学及其相对生物利用度。方法 :18名健康志愿者单剂量口服不同生产厂家的头孢氨苄胶囊 ,以反相高效液相色谱法测定其血药浓度经时过程。结果 :受试制剂和参比制剂中头孢氨苄主要药物动力学参数分别为 :Tmax为 (1.14± 0 .31)、(0 .83± 0 .2 3) h,cmax为 (18.81± 5 .16 )、(2 1.2 4± 4 .71)μg/ m l,t1 /2β为 (1.95±0 .11)、(1.89± 0 .11) h,AUC为 (47.85± 7.33)、(46 .91± 7.15 )μg· h· m l- 1 。 结论 :被试制剂与参比制剂是生物等效制剂。     

国产头孢氨苄片与国外同品种的人体生物等效性研究

目的 考察两种（国产与国外同品种）头孢氨苄片的人体生物利用度，评价两制剂在健康人体的生物等效性。方法将20例健康志愿者随机平均分为两组，交叉口服单剂量试验制剂（国产）和参比制剂头孢氨苄片（美国梯瓦制药生产）500 mg,停药清洗期为1周。采用高效液相色谱法测定血浆头孢氨苄浓度。结果单剂量口服试验制剂与参比制剂头孢氨苄片后，两药的主要药动学参数分别为tmax：(0.95±0.40)和（0.99±0.33）h；Cmax：（19.53±5.20）和（19.03±4.39）μg·mL-1；t1/2： (1.03±0.17)和(1.00±0.20) h；AUC0→6h：(33.26±6.60)和(33.39±6.39) μg·h·mL-1；AUC0→∞：(34.05±6.83)和(34.21±6.86) μg·h·mL-1。试验制剂与参比制剂比较,人体相对生物利用度为(99.8±8.0) %。 试验制剂的AUC0→6h和AUC0→∞90%可信区间分别为96.4%～102.6%和 96.5%～102.6%；Cmax的90%可信区间为94.6%～109.4%。两制剂tmax差异无显著性（P＞0.05）。结论单剂量口服试验或参比制剂后，两制剂的主要药代动力学参数Cmax、AUC0→6h、AUC0→∞和tmax均差异无显著性，国产头孢氨苄片与美国梯瓦制药生产的头孢氨苄片具有生物等效性。     

苦参素分散片和苦参素胶囊的人体生物等效性研究

目的:评价苦参素分散片和苦参素胶囊的人体生物等效性。方法:18名男性健康志愿者随机交叉口服苦参素分散片和苦参素胶囊各300 mg,采用液相色谱-串联质谱法(LC-MS／MS)测定血药浓度。用DAS软件计算药动学参数,考察其生物等效性。结果:受试苦参素分散片和参比苦参素胶囊的tmax分别为(2．4±s 0．9)h和(2．2±0．7)h;cmax分别为(268±187)μg·L-1和(265±173)μg·L-1;AUC0～10分别为(866±751)μg·L-1·h和(796±557)μg·L-1·h;AUC0-∞分别为(925±770)μg·L-1·h和(847±563)μg·L-1·h。以AUC0～10。计算,受试苦参素分散片和参比苦参素胶囊比较的人体相对生物利用度为(107±35)％。结论:受试制剂苦参素分散片和参比制剂苦参素胶囊具有生物等效性。     

盐酸头孢他美酯分散片人体药物动力学及生物等效性研究

目的研究盐酸头孢他美酯分散片在健康人体内的药物动力学,并评价其与同剂量的普通片剂的生物等效性。方法18名健康男性志愿者采用随机交叉自身前后对照口服盐酸头孢他美酯供试制剂或参比制剂500 mg,用高效液相色谱法测定盐酸头孢他美血药浓度,计算药物动力学参数和相对生物利用度,评价两种制剂的生物等效性。结果供试制剂和参比制剂的AUC0~12分别为(16.61±6.68)、(15.58±7.25)μg.h.mL-1,AUC0~∞分别为(18.00±7.01)、(16.93±7.55)μg.h.mL-1,Cmax分别为(3.10±1.24)、(2.95±1.30)μg.mL-1,tmax分别为(2.11±0.53)、(2.64±0.23)h,t1/2分别为(2.61±0.50)、(2.65±0.61)h。相对生物利用度为109.1%±14.0%。结论盐酸头孢他美酯分散片具有崩解快、吸收快的特点,相同剂量的分散片和普通片生物等效。     

阿莫西林/克拉维酸钾(7:1)分散片生物等效性研究

目的研究阿莫西林/克拉维酸钾(71)的国产分散片与进口干混悬剂的生物等效性.方法20例健康男性志愿者采用双周期随机交叉、单剂量口服国产阿莫西林/克拉维酸钾分散片(71)和进口干混悬剂(71)2种制剂,服药剂量均为阿莫西林800mg和克拉维酸114mg.用HPLC法测定血清中阿莫西林和克拉维酸的浓度,并用3P97程序对试验数据进行处理.结果国产分散片和进口干混悬剂中阿莫西林Cmax分别为(12.39±3.22)和(12.32±3.27)μg@mL-1;Tmax分别为(1.28±0.40)和(1.24±0.36)h;AUC0-6分别为(31.91±7.36)和(30.84±6.61)μg@h@mL-1;国产药与进口药比较,阿莫西林相对生物利用度F0-6为(103.56±8.33)%.国产分散片和进口干混悬剂中克拉维酸Cmax分别为(2.594±1.044)和(2.505±0.949)μg@mL-1;Tmax分别为(1.06±0.43)和(1.05±0.52)h;AUC0～6分别为(5.66±1.74)和(5.57±1.73)μg@h@mL-1;国产药与进口药比较,克拉维酸相对生物利用度F0-6为(102.49±13.55)%.结论国产阿莫西林/克拉维酸钾分散片和进口干混悬剂具有生物等效性.     

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.     

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.