阿斯咪唑混悬剂的人体药代动力学

目的比较国产、进口阿斯咪唑混悬剂在健康中国人体的药代动力学。方法用放射免疫法测定血浆阿斯咪唑 去甲阿斯咪唑含量 ,按交叉设计法对国产和进口阿斯咪唑混悬剂进行健康中国人体的药代动力学的比较,并求相对生物利用度。结果经3P87软件处理 ,阿斯咪唑的药代动力学呈二室模型。主要药代动力学参数 :国产剂 :Vd=6.88±1.36L;αT1/2=4.24±4.06h;βT1/2=170.31±73.80h;CL=0.067±0.023ng/ml;Tpeak=1.00±0.53h;Cmax=1.25±0.17ng/ml;AUC=162.97±48.57ng/ml·h-1。进口片 :Vd=6.40±3.07L;αT1/2=1.31±0.91h;βT1/2=156.02±120.74h;CL=0.079±0.045ng/ml;Tpeak=1.00±0.53h;Cmax=1.08±0.19ng/ml;AUC=173.46±114.66ng/ml·h-1。结论国产、进口阿斯咪唑混悬剂在中国人体的药代动力学参数均未发现明显差异。     

阿斯咪唑片剂人体药代动力学和生物利用度的初步研究

目的：观察阿斯咪唑片剂的人体药代动力学和生物利用率。方法：用放射免疫法测定血浆阿斯咪唑＋去甲阿斯咪唑含量，按交叉设计法对国产和进口阿斯咪唑片进行健康中国人体的药物代谢学比较研究，并求得相对生物利用率。用3P87软件处理，结果与结论：阿斯咪唑的药代动力学呈二室模型。主要药代动力学参数：国产片：Vd=5.34±1．85L;αT1／2＝0．74±0．37h;βT1／2＝286．10±220．11h；CL＝0．052±0．031ng/ml;Tmax=1.56±1．32h;Cmax=1.04±0．10ng/ml;AUC=262.69±162．18ng/ml·h^-1。进口片：Vd=8.24±2．56L；αT1／2＝1．16±0．98h;βT1／2＝260．38±260．37h；CL＝0．089±0．079ng/ml;Tmax=1.37±0．82h;Cmax=0.93±0．14ng/ml;AUC=250.66±148．05ng/ml·h^-1。国产片对进口片的相对生物利用率为127．8％。     

阿斯咪唑混悬剂的人体药代动力学

目的 比较国产、进口阿斯咪唑混悬剂在健康中国人体的药代动力学。方法 用放射免疫法测定血浆阿斯咪唑＋去甲阿斯咪唑含量，按交叉设计法对国产和进口阿斯咪唑混悬剂进行健康中国人体的药代动力学的比较，并求相对生物利用度。结果 经3P87软件处理，阿斯咪唑的药代动力学呈二室模型，主要药代动力学参数：国产剂：V =6.88±1.36L;αT1/2=4.24±4.06h;βT1/2=170.31±71.80h;CL=0.067±0.023ng/ml；Tpeak=1.00±0.53h；Cmax=1.25±0.17ng/ml;AUC=162.97±48.57ng/ml·h^-1。进口片：Vd=6.40±3.07L;αT1/2=1.31±0.91h;βT1/2=156.02±120.74h;CL=0.079±0.045ng/ml;Tpeak=1.00±0.53h;Cmax=1.08±0.19ng/ml;AUC=173.46±114.66ng/ml·h^-1。结论 国产、进口阿斯咪唑混悬剂的中国人体的药代动力学参数均未发现明显差异。     

健康志愿者口服氨氯地平片的药代动力学和生物等效性研究

目的:研究氨氯地平进口片和国产片在健康志愿者体内的药代动力学及相对生物利用度.方法:单次口服10mg氨氯地平片,用高效液相色谱法测定血药浓度,3p97程序处理数据.结果:两种制剂降压平稳,72 h内均有降压作用.受试制剂和参比制剂的主要药代动力学参数,峰时间(Tmax)分别为(5.22±1.70),(5.89±1.28)h;峰浓度(Cmax)分别为(6.98±1.30),(6.95±1.15)ng/mL;消除半衰期[T1/2(he)]分别为(38.02±7.30),(41.03±11.62)h;药时曲线下面积(AUC0-72)分别为(244.96±55.80),(243.68±46.87)ng·h/mL;氨氯地平国产片的相对生物利用度平均为(100.7±12.5)%.结论:两种制剂生物等效.     

国产苯扎贝特片人体相对生物利用度的研究

目的:观察20名男性健康志愿者随机交叉口服单剂量200mg国产和进口苯扎贝特片后血药浓度变化,进行药代动力学和相对生物利用度研究;方法:用反相高效液相色谱测定苯扎贝特血药浓度,用3P87药代动力学程序计算有关药代动力学参数,其主要药代动力学参数经三因素方差分析;结果:国产和进口苯扎贝特片的血药浓度-时间曲线均符合口服吸收一室模型,主要药代动力学参数Tmax分别为2.38±0.89 h和2.16±0.79 h,Cmax分别为6.22±1.30mg·L-1和6.57±1.23 mg.L-1,T1/2分别为1.67±0.43h和1.49±0.35h,AUC0→12分别为20.32±3.98 mg·h·L-1和19.80±3.65 mg·h·L-1;两种制剂的主要药代动力学参数均无显著性差异(P>0.05);结论:以进口片为标准参比制剂,国产片的相对生物利用度为102.6±8.3%,双单侧t检验结果提示,两种制剂生物等效.     

国产盐酸二苯美仑片剂的人体相对生物利用度研究

8名男性健康受试者交叉口服150mg国产与进口盐酸二苯美仑片剂,进行国产片的药代动力学和相对生物利用度研究.血药浓度采用高效液相色谱法测定.结果表明:国产和进口片剂的血药浓度时间曲线符合血管外给药一室模型,国产片和进口片的主要药代动力学参数Cmax分别为11.35±8.03和14.74±11.12 μg·L-1,Tpeak分别为3.22±0.89和2.85±1.86 h,T1/2Ke分别为2.76±0.91和3.01±1.24 h, AUC分别为110.80±78.06和114.71±81.79 μg·h·L-1.两种片剂的药代动力学参数经统计学分析无显著性差异(P＞0.05).国产盐酸二苯美仑片剂的相对生物利用度为98.96%±23.41%.结果提示国产与进口制剂基本生物等效.     

国产盐酸曲马多栓的人体药代动力学和相对生物利用度研究

随机交叉直肠给予12名健康男性受试者100 mg进口和国产盐酸曲马多栓.采用气相色谱法测定给药后不同时间的血浆药物浓度,研究国产盐酸曲马多栓在人体内的药代动力学和相对生物利用度.研究结果表明:进口和国产盐酸曲马多栓的药代动力学参数(均数±标准差):Tmax分别为2.6±1.0 和2.7±1.1 h;Cmax分别为384 ±67和392 ±71 μg·L-1;T1/2分别为8.7 ±2.5和8.9±2.6 h;Vd/F分别为4.2 ±1.2 和4.4±1.3 L·kg-1;CL/F分别为22.8±10.9和22.8±9.2 L·h-1;AUC0～48分别为4792±1576和4719±1589 μg·h·L-1.经配对t检验上述参数差异均无显著性意义.国产盐酸曲马多栓相对生物利用度F为98% ±10%;其90%的可信区间为93%～113% .结果提示国产盐酸曲马多栓和进口盐酸曲马多栓具有生物等效性.     

国产与进口班布特罗片的人体生物等效性研究

目的:研究国产班布特罗口腔崩解片在人体的相对生物利用度,并与进口片比较,评价两者生物等效性。方法:20例健康男性志愿者随机交叉单剂量口服国产盐酸班布特罗口腔崩解片(受试制剂)或进口盐酸班布特罗片(参比制剂)20 mg后,采用液相色谱串联质谱法测定血浆中班布特罗及其代谢产物特布他林的血药浓度,用DAS 2.0软件计算药代动力学参数,并评价其生物等效性。结果:受试制剂和参比制剂药代动力学参数为:Cmax(6.22±1.51)和(5.96±1.39)ng.mL-1;Tmax(2.52±0.72)和(2.70±0.86)h;t1/2(11.06±3.60)和(10.64±2.24)h;AUC0～72 h(56.69±16.82)和(52.86±14.57)ng.h.mL-1。特布他林药代动力学参数:Cmax(10.04±2.92)和(9.38±2.87)ng.mL-1;Tmax(4.35±1.04)和(4.60±1.14)h;t1/2(19.60±4.26)和(18.27±4.22)h;AUC0～72 h(199.60±68.89)和(179.55±50.18)ng.h.mL-1。国产盐酸班布特罗口腔崩解片单次给药后的相对生物利用度为(107.4±16.9)%(班布特罗),(110.9±18.6)%(特布他林)。结论:国产班布特罗口腔崩解片与进口班布特罗片在人体内生物等效。     

愈美干混悬剂在健康志愿者体内的生物等效性研究

目的：建立高效液相色谱-荧光法（HPLC-FD）测定血浆中氧去甲右美沙芬1和愈创木酚甘油醚2的血药浓度,并研究愈美干混悬剂的相对生物利用度及生物等效性。方法：20名健康志愿者分两组,随机、交叉口服单剂量愈美干混悬剂（受试制剂）和愈美片（参比制剂）,HPLC法测定血药浓度,计算药代动力学参数及生物等效性评价。结果：受试制剂与参比制剂血浆中氧去甲右美沙芬的T1/2：（4.13±0.87）h和（3.48±1.18）h;Cmax：（1 136.79±242.38）ng/ml和（1 069.79±237.26）ng/ml;Tmax：（1.65±0.33）h和（2.08±0.44）h;AUC0-t：（5 893.07±938.43）ng.h/ml和（5 601.46±873.04）ng.h/ml;愈创木酚甘油醚的T1/2：（0.88±0.10）h和（0.86±0.23）h;Cmax：（1 495.27±319.32）ng/ml和（1 432.73±296.47）ng/ml;Tmax：（0.61±0.13）h和（0.71±0.12）h;AUC0-t：（2 091.43±413.87）ng.h/ml和（2 056.16±424.27）ng.h/ml。愈美干混悬剂的相对生物利用度氧去甲右美沙芬为（105.60±9.90）%,愈创木酚甘油醚为（102.10±6.80）%。结论：两制剂生物等效。     

国产与进口盐酸西替利嗪片的人体生物等效性评价

目的 :比较国产与进口两种盐酸西替利嗪片剂在健康成年男性志愿者体内的药代动力学和生物利用度。方法 :12名健康志愿者采用2周期随机交叉设计自身对照试验法 ,口服进口与国产盐酸西替利嗪片各10mg ,以反相高效液相色谱法测定血浆中药物浓度。结果 :国产西替利嗪与进口西替利嗪的主要药代动力学参数如下 :Cmax 分别为 (429 00±108 80)ng/ml和 (469 82±113 83)ng/ml,Tmax 分别为 (0 90±0 51)h和 (0 91±0 40)h ,以梯形法计算AUC0～36 分别为 (3312 72±682 39)ng/(ml·h)和 (3417 11±517 42)ng/(ml·h)。国产西替利嗪相对生物利用度为 (97 21±13 32) %。主要药代动力学参数经方差分析和双单侧t检验证明 ,无显著性差异 (P>0 05)。结论 :国产西替利嗪与进口西替利嗪在受试者体内的药代动力学参数相似 ,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.     

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.