尼莫地平胶囊健康人体生物等效性研究

目的　研究尼莫地平在健康人体的药动学和相对生物利用度。方法　 8名健康受试者单剂量随机交叉口服尼莫地平标准参比制剂和被测制剂 12 0mg ,采用HPLC法测定用药后不同时间的血药浓度。结果两种制剂的体内过程均符合一房室开放模型 ,AUC分别为 (190 4 1± 2 6 5 0 ) μg·h·L-1和 (186 2 4± 2 7 80 ) μg·h·L-1,Cmax分别为 (5 7 15± 7 4 1) μg·L-1和 (5 4 94± 10 0 0 ) μg·L-1,Tmax分别为 (0 97± 0 14 )h和 (1 0 1± 0 18)h。被测制剂的相对生物利用度为 (98 0 1± 9 5 1) %。结论　用NDST软件对两种制剂的AUC、Cmax、Tmax等进行双向单侧t检验 ,表明两种制剂具有生物等效性     

国产盐酸氨溴索胶囊人体生物等效性

目的 :研究被试制剂国产盐酸氨溴索胶囊和标准参比制剂 (沐舒坦R○)的药动学和人体生物等效性。方法 :采用高效液相色谱法测定 12名健康受试者单剂量口服被试制剂或参比制剂 90mg后 ,血浆中盐酸氨溴索的浓度 ,经 3p97计算程序拟合 ,计算其药动学参数 ,比较其与标准参比制剂的人体生物等效性。结果 :经 3p97计算程序拟合 ,两者在体内的过程皆符合血管外给药一室模型 ,采用梯形法计算的两者AUC0 -t均值分别为 (2 42 1.2± 76 1.3) μg·h·L-1和 (2 485 .9± 80 3 .9) μg·h·L-1,实测Cmax均值分别为 (385 .5± 98.3) μg·L-1和 (378.9± 90 .3) μg·L-1,实测Tpeak均值分别为 (1.5± 0 .3)h和 (1.6± 0 .4)h。被试制剂的相对生物利用度为 (97.9± 6 .7) %。结论 :经统计学分析 ,被试制剂和标准参比制剂具有生物等效性     

非那雄胺2种片剂的人体生物等效性研究

目的 :研究 2种非那雄胺片的药动学和相对生物利用度 ,评价其生物等效性。方法 :采用随机交叉试验设计 ,2 2名健康男性志愿受试者单剂量口服 4 0mg受试品和参比品 ,以RP -HPLC法测定血药浓度。结果 :受试品和参比品的药动学参数分别AUC0 2 4 为 (15 97±s 6 10 ) μg·h·L- 1和 (15 6 9± 6 2 9)μg·h·L- 1,AUC0 ∞ 为 (16 80± 6 0 7) μg·h·L- 1和(16 75± 6 2 8) μg·h·L- 1,Tmax 为 (2 .4± 0 .3)h和(2 .3± 0 .3)h ,Cmax为 (2 80± 112 ) μg·L- 1和 (2 84±110 ) μg·L- 1,T1/ 2 分别为 (2 .9± 0 .8)h和 (3.3±1.0 )h。以进口分装非那雄胺 (商品名保列治 )片为参比制剂 ,非那雄胺片生物利用度F0 2 4 为 (10 3±18) % ,F0 ∞ 为 (10 1± 16 ) %。结论 :方差分析及双单侧t检验表明 ,2种制剂具有生物等效性。     

HPLC/MS研究国产盐酸班布特罗片及其代谢物特布他林人体生物等效性

目的　研究国产班布特罗片剂和进口片剂进行人体生物等效性研究。方法　 2 0名健康受试者随机交叉给药 ,用液相色谱 /质谱联用测定血浆中班布特罗其代谢物特布他林的浓度。结果　经数据处理 ,单次口服国产和进口班布特罗片剂后班布特罗的药代动力学参数 :AUC0 -t分别为 (5 2± 2 1) μg·h·L-1和 (5 1± 2 0 ) μg·h·L-1,Tmax分别为 (2 9± 0 9)h和 (2 6± 0 7)h ,Cmax分别为 (6 0± 2 6 ) μg·L-1和 (6 2± 2 9) μg·L-1。特布他林 :AUC0 -t分别为 (191± 30 ) μg·h·L-1和 (197± 37) μg·h·L-1,Tmax分别为 (4 2± 1 0 )h和 (4 2± 1 0 )h ,Cmax分别为 (10± 5 )μg·L-1和 (10± 4) μg·L-1。国产班布特罗片剂单次给药后的相对生物利用度为 10 2 %± 8% (班布特罗 ) ,10 0 %±12 % (特布他林 )。结论　经统计学证明两制剂有生物等效性     

阿那曲唑片的人体生物利用度测定(英文)

目的 :评价国产和进口阿那曲唑片的生物等效性。方法 :2 0名受试者随机分成 2组 ,交叉口服试验品与对照品各 1片 (1mg× 1片 ) ,用气相色谱法测定血药浓度。方法线性范围为 0 .5～ 2 0 0 .0μg·L- 1血浆 (r =0 .9997,n =90 ) ,低、中、高浓度(1.0 ,10 .0 ,2 0 .0 μg·L- 1血浆 )方法回收率分别为93.50 % ,10 0 .17% ,98.96 %。天内与天间精密度均小于 13%。结果 :试验片与对照片相比 ,其Tmax分别为 1.2h± 0 .5h和 1.3h± 0 .4h ,Cmax分别为10 μg·L- 1± 3μg·L- 1和 10 .2 μg·L- 1± 2 .5μg·L- 1,AUC0 T 分别为 386 μg·L- 1± 117μg·L- 1和385μg·L- 1± 117μg·h- 1·L- 1,T1/ 2 分别为 36h±14h和 32h± 10h。试验片平均相对生物利用度(10 0± 9) % (n =2 0 ,以AUC0 T计算 )。结论 :试验片与对照片两者生物等效。     

国产亚叶酸钙片、胶囊与进口亚叶酸钙片的人体相对生物利用度比较

目的 :研究 3种亚叶酸钙制剂 (国产片剂、胶囊和进口片剂 )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 ,测定血浆中亚叶酸钙浓度 ,计算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、胶囊和进口片单剂量 75mg ,po后 ,Tmax 分别为 ( 2 .5±s0 .3)h ,( 2 .5± 0 .3)h和 ( 2 .4± 0 .3)h ;Cmax为 ( 654± 146) μg·L- 1,( 599± 132 ) μg·L- 1和 ( 640± 163)μg·L- 1;AUC0～∞ 为 ( 7811± 1481) μg·h·L- 1,( 70 91± 1397) μg·h·L- 1和 ( 7898± 1855) μg·h·L- 1;T12 为 ( 8.7± 0 .6)h ,( 8.6± 0 .4 )h和 ( 8.6±0 .5)h。国产片、胶囊相对生物利用度分别为 ( 10 1± 14) % ,( 93± 11) %。结论 :3种制剂生物等效。     

头孢克罗片在人体中的相对生物利用度

目的　 研究头孢克罗片的人体相对生物利用度。 方法 　采用微生物法测定不同时间头孢克罗在人体的血药浓度 ,计算被试制剂人体相对生物利用度。 结果 　被试制剂和参比制剂的头孢克罗的血药浓度峰值时间分别为 0 98± 0 0 3h和 0 83± 0 10h ,峰浓度分别为 9 87± 0 94μg·ml- 1 和 10 0 8± 1 16 μg·ml- 1 ;药时曲线下面积分别为 16 30± 2 14μg·h·ml- 1 和 18 2 2± 3 47μg·h·ml- 1 。 结论 　头孢克罗片剂人体相对生物利用度为 (90 5 2±6 80 ) %。被试制剂和参比制剂体内生物作用等效     

尼莫地平片的药动学及生物等效性

目的 :研究尼莫地平片的药动学和相对生物利用度 ,验证该制剂与进口尼莫地平片的生物等效性。方法 :采用HPLC法测定 2 4名健康男性志愿者自身交叉单剂量口服国产尼莫地平片和进口尼莫地平片 12 0mg的经时血药浓度 ,计算主要药动学参数以及受试制剂的生物利用度。结果 :国产尼莫地平片和进口尼莫地平片的血药浓度 时间曲线符合一室模型 ,其主要药动学参数 :Cmax分别为 (83.9± 15 .4) μg·L-1与 (83.5± 12 .8) μg·L-1,Tmax分别为 (0 .5 7± 0 .0 6 )h与 (0 .6 7± 0 .0 8)h ,T1/2ke分别为 (1.80± 0 .16 )h与 (1.6 9± 0 .17)h ,AUC0 -t分别为 (16 0 .9± 15 .8) μg·h·L-1与 (15 6 .2± 18.7) μg·h·L-1。国产尼莫地平片对进口尼莫地平片的相对生物利用度为 (10 8.0± 7.2 ) %。结论 :国产尼莫地平片与进口尼莫地平片生物等效     

氯雷他定片在健康志愿者的药代动力学与生物等效性研究

目的比较深圳市海滨制药有限公司研制的氯雷他定片(受试制剂)和上海先灵葆雅制药有限公司生产的氯雷他定片(商品名开瑞坦,参比制剂)在健康人体内的药代动力学过程,并评价两制剂的生物等效性.方法20例健康男性受试者随机交叉单次口服氯雷他定片40 mg后,采用固相萃取反向HPLC法测定氯雷他定血浆浓度,进行有关生物利用度研究,并评价二者的生物等效性.结果单次口服参比与受试氯雷他定片40 mg后,主要药代动力学参数Cmax分别为34.9±16.6 μg·L-1与33.5±17.4μg·L-1,tmax分别为0.76±0.24h与0.75±0.26h,f1/2分别为1.63±0.48h与1.73±0.49h,AUC0-m分别为53.7±25.9μg·h·L-1与48.8±21.0μg·h·L-1,AUC0→∞分别为58.5±28.01μg·h·L-1与54.6±23.8μg·h·L-1.受试制剂相对于参比制剂的生物利用度F为94.5%±14.5%.结论统计分析结果显示,受试制剂与参比制剂生物等效.     

多西环素肠溶微粒胶囊与片剂的人体生物等效性

目的 :研究多西环素肠溶微粒胶囊和多西环素片的人体生物等效性与药动学。方法 :2 0名男性健康志愿者随机分 2组 ,按双周期交叉口服单剂量 2 0 0mg多西环素的 2种制剂 ,分别于服药前及服药后 0 5 ,1,1 5 ,2 ,2 5 ,3,4,6 ,8,12 ,2 4,48,72h取血样 ,以HPLC法测定血浆中多西环素浓度 ,计算 2种制剂相对生物利用度参数 ,并评价其生物等效性。结果 :口服受试制剂多西环素肠溶微粒胶囊和参比制剂多西环素片的药动学参数 :cmax分别为 (3 6 5± 0 81) μg·mL-1和 (3 6 5± 0 73) μg·mL-1,tmax分别为 (2 5± 0 3)h和 (2 2± 0 7)h ,T1/ 2 (消除半衰期 )分别为 (2 1 4 8± 3 2 0 )h和 (2 1 85± 3 11)h ,AUC0→ 72 分别为 (72 18±2 2 6 8) μg·h·mL-1和 (72 0 6± 2 1 0 8) μg·h·mL-1,AUC0→∞ 分别为 (81 4 4± 2 4 94) μg·h·mL-1和 (81 82± 2 3 19) μg·h·mL-1,多西环素肠溶微粒胶囊相对生物利用度为 (10 1 9± 2 5 2 ) %,对参数cmax,AUC0→ 72 先进行方差分析 ,再进行双单侧t检验 ,表明 2种制剂的参数生物等效 ,tmax经非参数检验表明无统计学差异。结论 :多西环素肠溶微胶囊和多西环素片具有生物等效性。     

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.