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     

2种盐酸阿呋唑嗪制剂的生物等效性研究

目的:比较盐酸阿呋唑嗪缓释片和盐酸阿呋唑嗪进口普通片的人体生物等效性。方法:20名健康男性志愿者自身交叉单剂量口服盐酸阿呋唑嗪缓释片和盐酸阿呋唑嗪进口普通片5mg,用高效液相色谱法测定人血浆中盐酸阿呋唑嗪浓度,计算药动学参数,并进行统计学分析及生物等效性评价。结果:盐酸阿呋唑嗪缓释片和盐酸阿呋唑嗪进口普通片的Cmax分别为(28·92±9·63)、(32·92±10·23)μg·L-1,tmax分别为(2·7±0·6)、(1·4±1·0)h,AUC0～∞分别为(221·14±59·46)、(245·68±67·20)μg·h·L-1,t1/2分别为(6·68±0·85)、(4·73±1·22)h,AUC0～24分别为(215·20±49·63)、(226·30±53·60)μg·h·L-1。盐酸阿呋唑嗪缓释片的相对生物利用度为(92·2±13·2)%。结论:2种制剂具有生物等效性。     

国产盐酸氟西汀胶囊的相对生物利用度

目的 :对国产盐酸氟西汀 (Flu)胶囊进行相对生物利用度研究。方法 :10名健康志愿者随机分成 2组 ,单剂量交叉服用国产及进口盐酸 Flu胶囊 40 m g,分别于 0、1、2、4、6、8、12 h及 1、2、3、4、7、18、2 8、42、5 6 d抽取血样 ,用高效液相色谱法检测Flu血药浓度 ;用 3P97软件计算药物动力学参数。结果 :国产及进口 Flu的主要药物动力学参数分别为 T1 /2β(2 9.7± 14.5 ) h、(32 .3± 7.3) h;tmax(6 .4± 2 .4) h、(6 .8± 2 .5 ) h;cmax(99.2± 2 4.3) nm ol/ L、(10 2 .3± 16 .8) nmol/ L ;AU C (5 0 0 9± 2 6 85 )、(5 42 8± 16 5 2 ) nmol/ L· h;差异均无统计学意义 (P>0 .0 5 ) ;国产 Flu的相对生物利用度为 (97.5± 2 2 .5 ) %。结论 :国产与进口盐酸 Flu胶囊为生物等效     

两种盐酸特拉唑嗪片的人体生物等效性研究

目的 评价单剂量口服国产和进口盐酸特拉唑嗪片的人体生物等效性。 方法 采用单中心、随机、开放、双周期交叉试验设计,21名受试者在不同周期分别空腹口服国产和进口盐酸特拉唑嗪片2 mg,于给药前0 h及给药后60 h内不同时间点采集静脉血4 ml,采用液-质联用(LC-MS/MS)法测定受试者血浆中特拉唑嗪的浓度。 结果 国产和进口盐酸特拉唑嗪片的t_1/2分别为(13.2±2.39)和(12.5±1.93) h;t_max分别为(1.01±0.83)和(1.08±0.69) h;C_max分别为(40.1±10.6)和(37.3±9.57) ng/ml;AUC_0-∞分别为(428±82.1)和(426±85.2) ng·h/ml。国产盐酸特拉唑嗪片的相对生物利用度为(101.2±14.7)%。国产与进口盐酸特拉唑嗪片AUC_0-t和C_max几何均值比的90%置信区间(CI)均落在80%~125%之间。 结论 国产和进口盐酸特拉唑嗪片具有生物等效性。     

进口与国产利鲁唑片剂的生物等效性

目的评价国产与进口利鲁唑片剂的生物等效性。方法20名健康志愿者单剂量随机交叉口服150 mg国产和进口利鲁唑片剂,血浆样品经C18小柱提取纯化,高效液相色谱-紫外检测器测定利鲁唑血药浓度。结果国产与进口利鲁唑片剂的药动学参数分别为:cmax(860.02±247.45)、(713.05±214.35)μg.L-1;tmax(0.9±0.4)、(1.1±0.5)h;AUC0→24(3 035.41±760.35)(、3 161.78±760.99)μg.h.L-1;AUC0→∞(3 172.83±804.46)(、3 396.09±742.35)μg.h.L-1;T1/2(5.82±1.16)(、7.51±2.30)h。国产利鲁唑片的相对生物利用度F0→24为(97.1±13.9)%。结论国产和进口利鲁唑片具有生物等效性。     

奥沙普秦分散片的人体相对生物利用度

目的 :研究奥沙普秦分散片在健康人体的相对生物利用度 ,为临床更合理用药提供理论依据。方法 :采用 HPL C法测定了 18名健康志愿者口服奥沙普秦分散片和普通片各 40 0 m g后不同时间的血药浓度 ,并进行生物等效性评价。结果 :奥沙普秦分散片剂和普通片的 cmax分别为 ( 70 .5 8± 7.6 0 ) ︼g/ml和 ( 6 5 .89± 8.2 2 ) ︼g/ml;tmax分别为 ( 3.2 2± 0 .43) h和 ( 3.44± 0 .5 1)h;T1 / 2 分别为 33.18h和 2 9.41h;AUC(0 - 96h) 为 ( 2 741.6± 393.6 )︼g/ml· h和 ( 2 5 6 1.8± 375 .7)︼g/ml· h。奥沙普秦分散片剂的人体相对生物利用度为 ( 10 4.0 2± 4.0 5 ) %。结论 :奥沙普秦分散片剂与普通片具有生物等效性。     

国产与进口马来酸咪达唑仑片的生物等效性

目的比较国产和进口马来酸咪达唑仑片在20名男性健康受试者中的药物动力学和相对生物利用度.方法采用反相高效液相色谱测定血浆中马来酸咪达唑仑的浓度,并用3P97程序拟合.结果单剂量po国产和进口马来酸咪达唑仑片15mg的AUC0～t分别为(587.86±161.65)、(579.99±151.25)h*mg/L;cmax是(220.57±67.64)、(199.18±60.53)mg/L;tmax为(1.58±0.59)、(1.30±0.44)h;T1/2为(2.94±1.40)、(3.26±1.37)h,国产和进口片剂的所有药物动力学参数经统计学处理均无显著性差异(P＞0.05).结论国产马来酸咪达唑仑片的相对生物利用度为(102.25±18.28)%,双单侧检验法证明,与进口片具有生物等效性.     

国产盐酸西替利嗪片和胶囊的人体药动学及相对生物利用度

目的 :研究国产盐酸西替利嗪片和胶囊的人体药动学和生物等效性。方法 :选择 2 1名男性健康志愿者 ,采用反相高效液相色谱法 ,以紫外 2 2 9nm为检测波长 ,测定了单剂量 (2 0mg)口服国产盐酸西替利嗪片、胶囊和进口盐酸西替利嗪片在人体内的西替利嗪浓度。结果 :盐酸西替利嗪的体内动态过程呈一级吸收的二房室开放模型 ,国产片、胶囊和进口片的Cmax分别为 (6 4 8.5± 117.6 ) ,(6 78.8± 10 4 .6 )和 (6 6 1.5± 12 0 .6 )ng·ml-1,Tmax分别为 (1.0± 0 .4 ) ,(1.2± 0 .5 )和 (1.1± 0 .4 )h ,t1/ 2 β分别为 (7.8± 2 .6 ) ,(7.6± 2 .7)和 (9.4± 5 .2 )h ,MRT分别为 (7.2± 0 .6 ) ,(7.3± 0 .6 )和 (7.4± 0 .4 )h ,AUC0→ 2 5分别为(45 0 3.3± 6 89.5 ) ,(46 0 1.2± 739.1)和 (484 0 .5± 937.1)ng·h-1·ml-1,AUC0→∞ 分别为 (5 0 34.4± 84 1.4 ) ,(5 12 9.6± 776 .2 )和(5 4 32 .8± 10 2 4 .0 )ng·h-1·ml-1。结论 :国产盐酸西替利嗪片和胶囊与进口片具有生物等效性     

盐酸氟桂利嗪片人体生物等效性研究

目的 :12名健康受试者随机自身交叉口服20mg盐酸氟桂利嗪片和孚瑞尔进行药代动力学和生物等效性研究。方法 :采用高效液相色谱荧光检测法 ,测定血浆中盐酸氟桂利嗪的浓度。结果 :经3p97生物利用度计算程序处理拟合 ,得盐酸氟桂利嗪片和孚瑞尔AUC0～∞ 分别为 (328 15±24 52) μg/ (h·L)和 (351 93±35 86) μg/ (h·L) ,Cmax 分别为 (39 41±5 67) μg/L和 (39 89±3 39) μg/L ,Tmax 分别为 (2 56±0 57)h和 (2 64±0 52)h ,经配对t检验 ,两者的主要药动学参数均无显著性差异 (P>0 05)。采用梯形法计算的盐酸氟桂利嗪片和孚瑞尔的AUC0～t 分别为 (360 40±23 50) μg/(h·L)和 (377 81±28 59) μg/(h·L)。结论 :经方差分析和双单侧检验 ,结果表明 ,两者具有生物等效性 ,盐酸氟桂利嗪片剂的相对生物利用度为 (95 7±6 6) %。     

国产阿呋唑嗪片剂健康人体生物等效性研究

目的研究国产阿呋唑嗪片剂的相对生物利用度并求证该制剂的生物等效性.方法采用随机交叉分组试验设计,18名成年健康男性受试者分别空腹口服单剂量国产阿呋唑嗪片(试验制剂)及进口片(参比制剂),采集12h内动态血标本,用反相HPLC法测定血浆药物浓度,计算两者的药代动力学参数及相对生物利用度,并求证国产片剂和进口片剂的生物等效性.结果口服阿呋唑嗪5mg国产及进口片剂的主要药代动力学参数t1/2β分别为3.19±0.60和2.96±0.39h,tmax分别为1.89±0.72和1.53±0.40h;c分别为18.40±5.94和18.99±7.39 μg@L-1;AUC0～12分别为78.70±118.19和78.57±20.46μg@h@L-1;AUC0～∞分别为87.45±19.05和86.34±29.60μg@h@L-1.经计算试验制剂与参比制剂的平均相对生物利用度AUC0～12为101.14%±7.70%,AUC00～∞为102.13%±9.21%.两种片剂的AUC0～12'AUC0～∞,Cmax经对数转换后多因素方差分析结果表明两制剂间无显著性差异(P＞0.05);经双单侧t检验接受两种片剂生物等效的假设;AUC0-1290%置信区间为96.08%～105.8%,AUC0～∞为96.97%～106.8%.且试验制剂AUC的90%可信区间落在标准参比制剂的80%～125%之间,故认为两者等效.结论国产与进口阿呋唑嗪片为生物等效制剂.     

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.