左旋氧氟沙星的人体相对生物利用度研究

目的比较国产盐酸左氧氟沙星胶囊(A)与进口左旋氧氟沙星片(可乐必妥片,B)的人体相对生物利用度.方法对10名男性健康志愿者交叉单剂量口服A和B各200mg后,采用HPLC测定不同时间血药浓度,绘制血药浓度-时间曲线,计算有关药物动力学参数和相对生物利用度.结果A和B两种制剂Cmax分别为(2153.5±624.5)ng/ml和(2083.0±716.6)ng/ml;Tmax分别为(0.75±0.35)h和(1.15±0.58)h,T1/2分别为(7.20±0.6)h和(7.67±1.2)h,AUC分别为(11656.5±2131.9)ng·h/ml和(11908.7±2491.2)ng·h/ml.经统计分析,两种制剂的药物动力学参数无显著性差异(P＞0.05).国产盐酸左氧氟沙星胶囊的相对生物利用度为(102.0±8.7)%.结论两种制剂体内生物作用等效.     

亚叶酸钙片的人体相对生物利用度

目的研究国产和进口亚叶酸钙片在12名健康志愿者体内的相对生物利用度.方法同体交叉试验后,血样采用固相萃取后经RP-HPLC法测定血浆中亚叶酸钙的浓度,计算两种片剂的主要药物动力学参数和相对生物利用度,并进行统计学分析.结果国产片和进口片单剂量po后,tmax分别为(2.4±0.3)和(2.3±0.3)h,cmax分别为(720±96)和(720±109.9)ng/ml,AUC0→t分别为(6382.3±1234.1)和(6287.7±1079.4)ng*h/ml,AUC0→∞分别为(7398.8±1331.5)和(7263.5±1225.3)ng*h/ml,MRT0→t分别为(5.88±0.17)和(5.84±0.31)h,T1/2分别为(8.69±1.09)和(8.40±1.21)h.国产片平均相对生物利用度为(101.7±9.6)%.结论两种片剂在健康志愿者体内为生物等效.     

佐米曲普坦片的人体生物等效性研究

目的:研究国产与进口佐米曲普坦片的人体生物等效性。方法:采用高效液相色谱-荧光法测定24名健康男性志愿者随机交叉单剂量口服佐米曲普坦片5mg后血浆中的药物浓度,计算其药动学参数及相对生物利用度。结果:口服佐米曲普坦片的药-时曲线符合线性动力学一室开放模型,国产及进口佐米曲普坦片的Cmax分别为(8.273±3.379)、(7.756±2.623)ng/ml,tmax分别为(2.341±1.169)、(2.644±1.121)h,AUC0～t分别为(47.95±15.75)、(46.27±13.71)(ng·h)/ml,国产制剂相对于进口制剂的人体生物利用度为(106.72±32.03)%。结论:国产与进口佐米曲普坦片具有生物等效性。     

吡咯地尔片的人体相对生物利用度研究

8名健康男性志愿者,按交叉设计单剂量po 200mg国产吡咯地尔片剂和进口Vascor片剂.高效液相色谱法测定血浆药物浓度,进行相对生物利用度研究.结果表明:国产和进口片剂的T_(max)分别为2.50±0.55h和2.54±0.48h,C_(max)分别为480.97±96.98ng/ml和494.38±64.10ng/ml,AUC分别为3.58±0.83μg·h·ml~(-1)和3.41±0.82μg·h·ml~(-1).药-时曲线符合一级吸收二室模型.经统计学检验.两种药品的各项药物动力学参数均无显著性差异(P>0.05);吡咯地尔片和Vascor片具有生物等效性,吡咯地尔片的平均相对生物利用度为105.3%.     

萘普生钠片的人体生物等效性

目的 :比较国产和进口萘普生钠片在 2 0名男性健康受试者间的药物动力学和生物等效性。方法 :随机交叉单剂量口服萘普生钠片 0 .5 5 g后 ,采用高效液相色谱 -荧光检测法测定血药浓度。结果 :国产和进口萘普生钠片的药物动力学参数如下 :AUC0 - t分别为 (975 .36± 176 .5 1)、(982 .5 5± 141.0 4) ︼g· h/ ml;cmax分别为 (72 .0 5± 13.95 )、(75 .6 2± 15 .0 5 ) ︼g/ m l;tmax分别为 (1.6 0± 1.17)、(1.15± 0 .5 9) h;T1 / 2 分别为 (11.6 9± 1.47)、(11.82± 1.38) h。经统计学处理 ,上述各项参数间差别均无统计学意义 (P>0 .0 5 )。国产萘普生钠片相对生物利用度为 (99.18± 9.93) %。结论 :萘普生钠片国产片与进口片具有生物等效性     

双氯芬酸钾胶囊人体药代动力学与相对生物利用度研究

目的 :研究双氯芬酸钾胶囊在正常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10名健康男性志愿者随机自身交叉单剂量口服50mg 双氯芬酸钾胶囊和进口双氯芬酸钾片后的血药浓度 ,计算两者的药代动力学参数及相对生物利用度 ,并以AUC(0～6) 、Tmax 、Cmax 为指标 ,用配对t检验法分析国产胶囊与进口片的生物等效性。结果 :国产与进口双氯芬酸钾制剂的药 -时曲线符合口服吸收一房室模型。AUC(0～6 ) 分别为 (1834 52±711 06) μg/(h·L)、(1891 19±859 08) μg/(h·L) ;Tmax 分别为 (1 15±0 77)h、(1 30±0 97)h ;Cmax 分别为 (1522 29±1063 87)ng/ml、(1508 54±892 44)ng/ml。配对t检验结果表明 ,AUC(0～6) Tmax、Cmax 均无显著性差异 (P>0 05)。结论 :国产双氯芬酸钾胶囊对进口片的相对生物利用度为 (100 80±16 59) % ,国产与进口两种双氯芬酸钾制剂具有生物等效性     

托吡酯片人体生物等效性研究

目的研究国产与进口托吡酯片口服给药后的人体生物等效性。方法采用两制剂双周期交叉试验设计,18名健康男性受试者分别单剂量口服国产或进口托吡酯片100mg,采用高效液相色谱-质谱法测定人血浆中托吡酯的浓度。结果国产片与进口片的Cmax分别为(1222±237)、(1274±180)μg/L,tmax分别为(1.5±1.0)、(1.2±0.9)h,AUC0~120分别为(40520±7524)、(40458±4731)(μg.h)/L,AUC0~∞分别为(44379±8082)、(44380±4952)(μg.h)/L,t1/2分别为(34.4±5.0)、(35.5±4.8)h;国产片的相对生物利用度为(100.8±19.2)%。结论国产与进口托吡酯片具有生物等效性。     

米诺环素胶囊对人体相对生物利用度的研究

目的研究国产和进口米诺环素胶囊在9例正常健康志愿者体内的相对生物利用度.方法采用随机交叉分组方法进行试验设计,血样中米诺环素浓度采用RP-HPLC法测定.采用PK-GRAPH药物动力学软件包进行数据处理,计算两种胶囊的主要药物动力学参数和相对生物利用度,并进行统计学分析.结果单剂量口服国产和进口米诺环素胶囊的药动学参数,曲线下面积(AUC)分别为74.5±17.9μg.h/ml和75.3±15.9μg.h/ml;表现分布容积(Vd)分别为45.6±7.8L和46.0±17.4L;清除率(CL)分别为2.8±0.6L/h和2.7±0.6L/h;半衰期(t1/2)分别为21.6±1.26 h和21.9±1.7 h;峰值时间(Tmax)分别为2.8±0.9h和2.4±0.9 h;峰值浓度(Cmax)为3.1±0.7μg/ml和3.1±0.6μg/ml.相对生物利用度为98.9%.上述参数与文献报道相似,经统计学检验,无显著差异.结论两种胶囊在健康志愿者体内是生物等效的.     

非那雄胺片的人体生物等效性研究

目的:研究国产与进口非那雄胺片的人体生物等效性。方法:采用高效液相色谱法测定18名健康男性志愿者随机交叉单剂量口服非那雄胺片10mg后血清中的药物浓度,计算药动学参数和相对生物利用度,并进行生物等效性评价。结果:国产及进口非那雄胺片的AUC0～t 分别为(990 .80±302. 80)、(1007 .46±333. 65) (μg·h)/L ,Cmax 分别为(119. 22±18. 48)、(114. 08±22 .97) μg/L ,tmax 分别为(2. 89±1. 02)h、(2. 64±0. 54)h ,国产制剂相对于进口制剂的人体生物利用度为(103. 35±29 .75) %。结论:国产与进口非那雄胺片具有生物等效性。     

国产和进口阿托伐他汀钙的药代动力学与相对生物利用度研究

目的通过研究国产和进口阿托伐他汀钙的药代动力学与相对生物利用度。方法 18例健康男性志愿者,随机分为两组,分别交叉口服国产和进口阿托伐他汀钙,用HPLC法测定血浆中阿托伐他汀钙的浓度,进行相对生物利用度的研究。结果口服20mg国产和进口阿托伐他汀钙的达峰时间(Tmax)分别为(1.7±0.5)h和(1.7±0.6)h;峰浓度(Cmax)(2.10±0.47)μg/L和(2.09±0.53)μg/L;消除半衰期(T1/2)分别为(2.97±1.09)h和(2.71±1.22)h;药时曲线下面积(AUC)分别为(10.88±2.60)μg/(h L)和10.56±2.23μg/(h L),经统计学分析两种制剂的药代动力学参数无显著性差异(P>0.05);国产和进口阿托伐他汀钙的相对生物利用度(104.7±5.6)%。结论两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.

---

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.     

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.     

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.     

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.