扎来普隆片的人体药动学及生物等效性评价

目的:评价扎来普隆片的生物等效性.方法:20例健康志愿者随机交叉自身对照,单剂量口服扎来普隆片剂和胶囊10mg后,血浆样品经液-液萃取后,以液相色谱荧光检测法测定浓度,进行人体相对利用度及生物等效性研究.结果:受试制剂扎来普隆片及参比制剂扎来普隆胶囊的Cmax分别为(35.01±9.01)和(34.63±12.75)μg·L-1,Tmax分别为(0.72±0.40)和(0.73±0.30)h,t1/2分别为(1.04±0.21)和(1.09±0.39)h,AUC0-t分别为(75.31±26.35)和(74.54±37.13)μg·h·L-1,主要药动学参数均无显著性差异(P>0.05 ).受试制剂与参比制剂的相对生物得用度为(105.94±17.69)%.结论:扎来普隆片与扎来普隆胶囊具有生物等效性.     

阿奇霉素分散片人体相对生物利用度及药动学

目的:研究受试制剂阿奇霉素分散片与参比制剂人体相对生物利用度及药动学.方法:20名健康受试者自身交叉单剂量口服阿奇霉素分散片受试制剂和参比制剂各500 mg,定时取血,用微生物法测定血药浓度.结果:受试制剂阿奇霉素分散片与参比制剂的血药浓度-时间曲线基本一致,符合一级吸收二房室模型.受试制剂与参比制剂的主要药动学参数分别为:消除半衰期t1/2β:(36.1±7.8)h,(39.9±10.3)h;Tmx:(2.4±0.5)h,(2.4±0.5)h;Cmax:(413.0±72.5)μg·L-1,(404.0±69.5)μg·L-1.药动学参数经配对t检验,P＞0.05,差异均无显著性.两种制剂的药时曲线下面积AUC0→t平均值分别为:受试制剂分散片(9 806±1 308)μg·L-1·h-1,参比制剂(9 949±1 395)μg·L-1·h-1;受试制剂分散片的相对生物利用度为:(99.0±9.0)%.结论:统计学结果表明,受试制剂阿奇霉素分散片与参比制剂生物等效.     

萘哌地尔胶囊和片剂的相对生物利用度

目的:研究萘哌地尔胶囊与片剂的生物等效性.方法:20名健康男性志愿者随机交叉口服单剂量(50 mg)萘哌地尔胶囊或片剂两种制剂,采用HPLC法测定血清中萘哌地尔的浓度.结果:口服萘哌地尔胶囊及片剂的Cmax分别为(51.0±16.3)μg·L-1和(52.7±18.2)μg·L-1;Tmax分别为(0.83±0.12)h和(0.80±0.10)h;T1/2β分别为(9.0±1.9)h和(8.9±2.3)h;AUC0-24分别为(176.3±37.1)μg·h·L-1和(174.4±42.7)μg·h·L-1;AUC0-∞分别为(202.4±48.3)μg·h·L-1和(197.0±45.4)μg·h·L-1;萘哌地尔胶囊对片剂的相对生物利用度为(103.6±14.8)%.结论:萘哌地尔胶囊和片剂具有生物等效性.     

托拉塞米胶囊与片剂在健康人体内的药动学和生物等效性

目的研究托拉塞米试验制剂(胶囊)和参比制剂(片剂)的人体药动学和生物等效性.方法20名健康受试者随机交叉口服托拉塞米胶囊(试验制剂)和托拉塞米片(参比制剂),剂量均为10 mg.血样加入内标(呋塞米)经预处理后采用HPLC法测定.结果试验胶囊、参比片剂的主要药动学参数Cmax分别为(1160.1±188.0),(1 271.2±326.8)μg·L-1;Tmax分别为(1.1±0.4),(1.0±0.4)h;t1/2分别为(4.1±1.0),(4.0±1.0)h;AUC0-t分别为(3 662.3±782.2),(3 783.2±1390.1)μg·h·L-1.以AUC0→t计算的试验胶囊的相对生物利用度为(100.6±23.9)%.结论经方差分析及双单侧t检验结果显示,试验制剂和参比制剂具有生物等效性.     

盐酸曲美他嗪胶囊的人体生物等效性

目的 评价国产盐酸曲美他嗪胶囊和进口盐酸曲美他嗪包衣片的人体生物等效性.方法 20名健康男性受试者按两制剂两周期的交叉试验设计单剂量口服20 mg的参比制剂和受试制剂后,采用LE-MS法测定血浆中盐酸曲美他嗪的浓度,使用DAS 1.0软件计算药动学参数并进行生物等效性统计分析.结果 参比制剂和受试制剂的ρmax分别为(55.9±9.2)和(56.4±12.2)μg·L-1;tmax分别为(2.5±0.8)和(2.7±0.9)h;AUC0→24h分别为(493.8±82.8)和(489.8±108.4)μg·h·L-1;AUC0→∞分别为(513.7±88.6)和(510.1±116.8)μg·h·L-1;t1/2分别为(4.8±0.4)和(4.7±0.4)h.双单侧t检验结果显示受试制剂的ρmax、AUC0→24h的90%置信区间分别为参比制剂相应参数的92.0%～108.4%和91.5%～105.3%,受试制剂的相对生物利用度为(99.6±16.5)%(以AUC0→24h计算).结论 国产盐酸曲美他啶胶囊与其进口包衣片具有生物等效性.     

奥昔布宁缓释胶囊与普通片的药动学及生物等效性

目的 研究健康志愿者单剂量和多剂量口服奥昔布宁缓释胶囊后的药动学特征,并评价奥昔布宁缓释胶囊与奥昔布宁普通片是否生物等效,为临床合理用药提供参考依据.方法 20名健康志愿者分别单剂量、多剂量口服试验缓释胶囊和参比普通片剂,于规定时间点取血,以LC-MS联用法测定奥昔布宁血药浓度,采用3P97软件计算各制剂单剂量和多剂量给药后的药动学参数.结果 单剂量给药,奥昔布宁缓释胶囊和普通片的ρmax分别为(8.27±7.28)μg·L-1和(17.16±12.17)μg·L-1;tmax分别为(2.55±0.85)h和(0.82±0.35)h;t1/2分别为(6.23±2.78)h和(5.54±2.18)h;AUC0→t分别为(51.94±40.27)μg·h·L-1和(49.8±434.33)μg·h·L-1;AUC0→∞.分别为(57.25±40.78)μg·h·L-1和(54.68±36.44)μg·h·L-1.奥昔布宁缓释胶囊相对于普通片生物利用度F0→1为(104.15±15.47)%.多剂量给药,奥昔布宁缓释胶囊和普通片的ρss max分别为(24.00±10.41)μg·L-1和(15.37±8.00)μg·L-1;ρss min分别为(1.59±0.80)μg·L-1和(1.33±0.80)μg‘L-1;ρss av分别为(5.01±2.22)μg·L-1和(2.49±1.17)μg·L-1;AUCss分别为(120.19±53.24)μg·h·L-1和(59.85±28.01)μg·h·L-1;DF分别为(446.23±135.27)%和(579.75±148.10)%;奥昔布宁缓释胶囊波动度明显小于普通片.结论 试验制剂具有缓释作用.试验制剂与参比制剂的ρmax生物不等效,但AUC0→t生物等效.     

国产与进口富马酸奎的平片的药动学比较及相对生物利用度

目的:研究富马酸奎的平片的药动学及相对生物利用度.方法:受试者交叉口服单剂量(100mg)国产片与进口片,用高效液相色谱法测定血药浓度.结果:两种片剂的主要药动学参数:Tmax分别为(1.7±0.8)h与(1.6±0.7)h,Cmax分别为(100.4±18 9)μg·L-1与(100.0±17.8)μg·L-1,AUC0-t分别为(246.8±29.4)μg·L-1·h与(244.7±28.8)μg·L-1·h,AUC0-∞分别为(250.7±30.2)μg·L-1·h与(248.9±29.6)μg·L-1·h,T1/2分别为(1.8±0.5)h与(1.8±0.4)h,国产片相对于进口片的生物利用度为(101.9±7.4)%.结论:两种制剂具有生物等效性.     

缬沙坦分散片与胶囊在健康人体的相对生物利用度研究

目的研究缬沙坦分散片和胶囊在人体内的相对生物利用度.方法 18名健康志愿者,采用自身对照,随机交叉方式分别口服缬沙坦分散片或胶囊160 mg后不同时间点取血,血浆样品以新建立的高效液相色谱-荧光检测法测定,比较两者主要药物动力学参数的差异和相对生物利用度.结果缬沙坦分散片和胶囊的AUC0～30均值分别为(17 268.2±5 611.6)、(17 723.1±5 844.2)μg·h·L-1,cmax均值分别为(2 185.9±656.9)、(2 176.5±730.7)μg·L-1,实测tmax均值分别为(1.2±0.5)、(2.2±0.4)h,方差分析结果表明,两种制剂的AUC0～∞、cmax没有显著性差异(P＞0.05),两制剂间的tmax有显著差异(P＜0.05),分散片明显快于胶囊剂.以胶囊为参比制剂,缬沙坦分散片的相对生物利用度为(98.8±14.6)%.结论缬沙坦分散片体内吸收快于缬沙坦胶囊,但血药浓度峰值和吸收程度没有显著性差异,两者仍具有生物等效性.     

奥美拉唑肠溶胶囊的人体生物等效性研究

目的:评价受试制剂奥美拉唑肠溶胶囊与参比肠溶胶囊的人体生物等效性.方法:22名健康男性受试者按照随机交叉试验设计,分别单剂量口服两种制剂40 mg,采用反相高效液相色谱法测定血浆中奥美拉唑的浓度,并用DAS 1.0软件对所得药代动力学参数进行统计分析.结果:受试者单剂量口服参比制剂和受试制剂后奥美拉唑的cmax分别为(0.93±0.57)和(0.98±0.52)μg/ml、tmax分别为(2.36±0.90)和(2.30±1.04)h,t1/2分别为(1.18±0.46)和(1.15±0.57)h、AUC0～8h分别为(2.48±2.09)和(2.48±1.98)μg·h·ml-1;AUC0～∞分别为(2.65±2.39)和(2.65±2.28)μg·h·ml-1.奥美拉唑肠溶胶囊的相对生物利用度为(111.1±58.1)%.结论:两制剂具有生物等效性.     

奥美拉唑肠溶胶囊的人体生物等效性研究

目的:评价受试制剂奥美拉唑肠溶胶囊与参比肠溶胶囊的人体生物等效性.方法:22名健康男性受试者按照随机交叉试验设计,分别单剂量口服两种制剂40 mg,采用反相高效液相色谱法测定血浆中奥美拉唑的浓度,并用DAS 1.0软件对所得药代动力学参数进行统计分析.结果:受试者单剂量口服参比制剂和受试制剂后奥美拉唑的cmax分别为(0.93±0.57)和(0.98±0.52)μg/ml、tmax分别为(2.36±0.90)和(2.30±1.04)h,t1/2分别为(1.18±0.46)和(1.15±0.57)h、AUC0～8h分别为(2.48±2.09)和(2.48±1.98)μg·h·ml-1;AUC0～∞分别为(2.65±2.39)和(2.65±2.28)μg·h·ml-1.奥美拉唑肠溶胶囊的相对生物利用度为(111.1±58.1)%.结论:两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.     

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.