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.     

青霉素V钾胶囊与片剂的药物动力学及相对生物利用度比较

目的比较青霉素V钾胶囊与片剂的药物动力学及相对生物利用度.方法以微生物法测定10名健康受试者单次空腹po青霉素V钾胶囊和片剂500mg后血、尿药浓度.结果po青霉素V钾胶囊和片剂后的体内过程符合二室模型.其平均cniax分别为(8.22±1.21)和(7.71±1.09)mg/L,tniax为(0.55±0.11)和(0.58±0.17)h,T1/2ka为(0.21±0.09)和(0.20±0.06)h,T1/2β为(0.81±0.21)和(0.72±0.08)h,AUC为(9.51±1.06)和(9.50±1.82)h@mg/L,24h累积尿排出率分别为给药量的(35.33±7.45)%和(37.80±5.45)%.青霉素V钾胶囊与片剂的药物动力学参数间差异无统计学意义(P＞0.05).结论青霉素V钾胶囊的相对生物利用度为(101.44士9.59)%,与片剂具生物等效性.     

国产青霉素V钾胶囊剂的药代动力学和生物利用度

本文用青霉素V钾胶囊剂与进口青霉素V钾片剂进行人体药代动力学和生物利用度研究.选择12名健康男性志愿者,采用自身交叉对照试验方法,分别单剂量一次口服青霉素V钾500mg,青霉素V钾血药浓度用微生物法测定,以枯草芽孢杆菌(63501)作为检定菌.青霉素V钾血药浓度--时间数据用3p87程序进行自动拟合并求算药代动力学参数,用NDST程序对AUC、Tmax和Cmax的实测值作生物等效性检验.结果:口服青霉素V钾片剂和胶囊剂两种制剂后青霉素V钾药代动力学参数分别为:T1/2:31.27±11.12min,27.57±6.46min(P>0.05);Cmax:9.14±3.07mg·L-1,9.69±2.66mg·L-1(P>0.05).青霉素V钾的相对生物利用度为97.99%±13.44%.结论:青霉素V钾的AUC、Tmax和Cmax经配对t检验、双单侧t检验、方差分析表明国产青霉素V钾胶囊剂与进口青霉素V钾片剂为等效制剂.     

国产氯沙坦钾胶囊的人体生物等效性研究

目的研究氯沙坦钾胶囊在20名健康志愿者体内的生物等效性。方法 20名健康男性志愿者采用随机交叉给药方案,分别单剂量口服50mg的氯沙坦钾国产制剂与进口制剂,采用反相高效液相色谱法测定血药浓度,利用DAS2.1软件处理数据,计算两者的药代动力学参数及相对生物利用度。结果口服50mg氯沙坦钾试验制剂(国产)及参比制剂(进口)后的主要药代动学参数如下:ρmax分别为(201.58±70.28)和(204.64±51.24)μg/L;tmax分别为(0.86±0.39)和(0.96±0.35)h;t1/2分别为(1.82±0.44)和(1.78±0.30)h;AUC0-8分别为(387.74±81.57)和(388.02±76.38)μg/(h L);AUC0-∞分别为(408.62±81.66)和(406.96±79.57)μg/(h L)。试验制剂(T)的相对生物利用度为(100.89±16.14)%。结论本法简便、灵敏、准确、稳定,可用于体内药物分析。国产氯沙坦钾胶囊与进口片剂具有生物等效性。     

国产尼莫地平分散片的药代动力学和生物利用度

目的以进口尼莫通片为对照,考察国产尼莫地平分散片的药代动力学和相对生物利用度。方法10名男性健康志愿受试者,随机交叉单剂量口服2种片剂各120mg,采用HPLC法测定血药浓度。结果经3P87程序处理,国产尼莫地平分散片的Tmax为（0.73±0.06）h,C     

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.     

替米沙坦片在健康人体的药代动力学和相对生物利用度

目的研究国产和进口替米沙坦片在健康人体的药代动力学并评价2制剂的生物等效性。方法20名健康志愿者单次、交叉口服替米沙坦片80mg后,用高效液相色谱-荧光检测法测定血浆替米沙坦浓度。用3P97药代动力学软件计算药代动力学参数。结果2种替米沙坦片在健康志愿者体内的药-时曲线均符合二室模型,2种制剂的主要药代动力学参数:Cmax分别为(944.71±376.08),(852.72±333.78)ng·mL-1;tmax分别为(0.98±0.60),(1.28±0.65)h;t1/2β分别为(28.78±13.88),(25.83±9.25)h;AUC0-t分别为(4.14±2.44),(3.83±1.97)mg·h·L-1;AUC0-∞分别为(4.64±2.84),(4.17±2.22)mg·h·L-1。国产对进口制剂的平均相对生物利用度F0-t为(99.64±23.93)%,F0-∞为(97.97±26.20)%。结论国产和进口替米沙坦片剂为生物等效制剂。     

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。     

单次口服国产红霉素环11,12-碳酸酯片剂药代动力学研究

目的通过对健康志愿者口服国产红霉素环酯片剂后的药代动力学研究,探讨国产红霉素环11,12-碳酸酯片剂在人体内的药代动力学特征.方法11名健康男性志愿者按拉丁方设计三种单剂量口服国产红霉素环11,12-碳酸酯片剂(250,500,750mg),用微生物琼脂平皿扩散法测定血清、尿液中药物浓度和排泄量,检测菌为藤黄八叠菌.结果受试者血药浓度-时间数据用3P97软件进行拟合,符合一室药代动力学模型,药代动力学参数如下t1/2分别为9.92±2.39,9.67±2.44和9.38±2.89h;tmax分别为7.27±3.26、6.00±1.26和7.64±2.94h;Cmax分别为0.35±0.16,0.62±0.18和1.08±0.42mg@L-1;AUC0-∞别为6.37±2.93,10.58±4.09和19.28±7.26mg@h@L-1.48h的尿累积排出百分率分别为8.76%±5.07%,7.89%±3.80%,10.22%±5.37%.结论与其他红霉素相比,本品具有分布广、排泄慢、尿累积排除率大等药代动力学特性,极有利于有关细菌感染的治疗.     

青霉素V钾健康人体药物动力学及相对生物利用度

以美国进口的青霉素 V钾片为标准参比制剂 ,研究国产青霉素 V钾片和胶囊在健康人体药物动力学及相对生物利用度。按 3制剂、3周期的 3× 3拉丁方试验设计 ,9名健康男性受试者 ,分别口服进口及国产青霉素 V钾 15 0 0 mg,采用微生物法测定血药浓度 ,用 3P87软件经微机处理药 -时数据。结果证明 ,进口及国产青霉素 V钾的体内过程均符合二房室模型 ,与标准参比制剂相比 ,两种被试制剂的 AUC、Cmax、Tmax均无显著差异 ,相对生物利用度分别为 10 2 .5 1± 11.0 9% (84.6 1%～ 114.49% )与 92 .5 0± 8.47% (82 .88%～10 6 .6 3% )。结论 :国产青霉素 V钾片和胶囊均具有生物等效性。     

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.     

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.