安吡昔康胶囊在健康志愿者体内的生物等效性

目的：测定人血浆中安吡昔康代谢物吡罗昔康的浓度,评价安吡昔康胶囊在健康志愿者体内的生物等效性。方法：20例健康志愿者,随机分成两组,分别单次口服27mg受试制剂安吡昔康胶囊和参比制剂安吡昔康片。采用HPLC-UV法测定给药后不同时间点血浆中的安吡昔康代谢物吡罗昔康血浓度,用DAS2.1软件计算其药代动力学参数,并作方差分析和双单侧t检验。结果：口服受试制剂和参比制剂后的T1/2为（49.19±11.50）和（47.85±9.86）h,Cmax为（1.885±0.361）和（1.90±0.40）mg.L-1,Tmax为（7.21±3.34）和（6.95±3.33）h,AUC0-216为（155.02±36.60）和（150.23±31.371）mg/L.h,AUC（0-∞）为（164.52±41.20）和（159.00±33.77）mg/L.h。结论：受试制剂安吡昔康胶囊的相对生物利用度为（103.9±17.0）%,两种制剂具有生物等效性。     

盐酸伐昔洛韦片的药动学及相对生物利用度

目的:研究盐酸伐昔洛韦片在健康人体的药动学和相对生物利用度。方法:采用两制剂双周期交叉对照的研究方法,以HPLC法测定18例健康志愿者单剂量口服盐酸伐昔洛韦片600mg后血浆中阿昔洛韦的浓度变化,采用DAS2.0软件计算药动学参数。结果:阿昔洛韦的线性范围为0.201～12.884mg.L-1(r=0.9999),日内和日间RSD均小于6.0%。供试制剂与参比制剂的主要药动学参数tmax分别为(1.5±0.6)h和(1.9±0.7)h;Cmax分别为(2.7±0.5)mg.L-1和(2.8±0.7)mg.L-1;t1/2分别为(3.0±0.6)h和(3.3±0.9)h;AUC0-t分别为(10.6±1.9).和(10.6±2.4)mg.L-1.h;AUC0-∞分别为(11.5±2.0)mg.L-1.h-1和(11.7±2.6)mg.L-1.h。两种盐酸伐昔洛韦片主要药动学参数间差异均无显著性(P>0.05)。供试制剂对参比制剂的相对生物利用度为(101.9±14.9)%。结论:供试制剂和参比制剂具有生物等效性。     

液-质联用测定氯诺昔康国产与进口片剂的人体生物等效性

目的:建立液相色谱-串联质谱法(LC-MS/MS)的检测方法,评价受试与参比的氯诺昔康片在健康人体的生物等效性。方法:采用随机、开放、双周期交叉试验设计,20名中国男性健康受试者单剂量口服受试制剂和参比制剂8 mg后不同时间点的血浆样本经甲醇直接沉淀蛋白,应用LC-MS/MS法测定氯诺昔康的血药浓度,利用DAS 2.0软件计算药动学参数,并进行生物等效性评价。结果:受试制剂和参比制剂的药动学参数如下:Cmax分别为(782.0±275.1)μg·L-1和(823.4±256.1)μg·L-1,tmax分别为(2.8±1.4)h和(2.6±1.4)h,t1/2分别为(3.5±1.2)h和(3.3±0.8)h,AUC0-24 h分别为(4 545±1 714)μg.h.L-1和(4 516±2 054)μg·h.L-1,相对生物利用度为(103.8±15.0)%。结论:建立的分析方法灵敏、简便、准确,统计结果表明受试制剂和参比制剂生物等效。     

富马酸异丙吡仑片的人体生物等效性

目的:研究富马酸异丙吡仑片的人体相对生物利用度。方法:健康志愿者20名,随机双交叉单剂量口服富马酸异丙吡仑试验和参比制剂,用高效液相色谱法测定血浆中异丙吡仑的浓度。用3p97药动学程序计算相对生物利用度和评价生物等效性。AUC0-36,AUC0-inf和Cm ax经方差分析和双单侧t检验,tm ax进行秩和检验。结果:单剂量口服试验制剂和参比制剂后血浆中的异丙吡仑的Cm ax分别为(1.10±0.14)mg.L-1和(1.09±0.15)mg.L-1;tm ax分别为(1.8±0.5)h和(1.9±0.6)h;AUC0-36分别为(9.1±1.9)mg.h.L-1和(9.2±2.3)mg.h.L-1;AUC0-inf分别为(9.6±2.0)mg.h.L-1和(9.9±2.4)mg.h.L-1;Cm ax、AUC0-36、AUC0-inf的90%可信区间分别为94.6%~107.1%、92.1%~106.1%、90.0%~106.2%。结论:试验制剂与参比制剂的人体相对生物利用度为(100.4±17.8)%,试验制剂和参比制剂具有生物等效性。     

美洛昔康胶囊人体生物等效性的研究

目的 评价美洛昔康胶囊(受试制剂)和美洛昔康片(参比制剂)在健康人体的生物等效性.方法 采用HPLC-UV法,测定人血浆中美洛昔康的浓度,并进行方法学验证;采用随机交叉自身前后对照试验设计,20名受试者分别口服受试制剂和参比制剂15 mg后,测定美洛昔康的血药浓度,计算药动学参数,评价两制剂的生物等效性.结果 美洛昔康胶囊和美洛昔康片的t1/2分别为24.61±10.46、26.56±7.57 h,Cmax分别为2.45±0.33、2.49±0.37 μg· mL-1,Tmax分别为4.58±1.35、5.05 ±1.51 h;AUC0→1分别为76.57±17.71、84.12±19.91 μg·h·mL-1.美洛昔康胶囊的相对生物利用度为92.8％±17.7％.结论 两制剂在健康中国人体内具有生物等效性.     

塞克硝唑片在健康人体的药动学及生物等效性

目的:研究塞克硝唑片在人体的药动学特点和生物等效性。方法:20名健康男性受试者,采用双周期交叉、自身对照试验设计,单剂量口服塞克硝唑受试制剂和参比制剂(沙巴克)2.0g,采用反相高效液相色谱法测定其血药浓度,计算其药动学参数和相对生物利用度,评价两种制剂的生物等效性。结果:塞克硝唑受试制剂和参比制剂的主要药动学参数:t1/2分别为(27.1±4.2)h和(26.6±4.7)h;tmax分别为(2.3±1.1)h和(2.9±1.1)h;Cmax分别为(49.6±6.4)mg.L-1和(46.2±4.2)mg.L-1;AUC0-96分别为(1 832.0±180.2)mg.L-1.h和(1 847.1±204.1)mg.L-1.h;AUC0-∞分别为(2 022.4±205.7)mg.L-1.h和(2 042.3±264.0)mg.L-1.h。方差分析结果表明,两种制剂的主要药动学参数之间差异无显著性。塞克硝唑受试制剂的相对生物利用度为(99.99±11.92)%。结论:经统计学分析,两种制剂具有生物等效性。     

HPLC-MS法测定人血浆中雷贝拉唑的浓度及其药动学

目的建立人血浆中雷贝拉唑的HPLC-MS测定方法,用其测定了志愿者口服雷贝拉唑钠肠溶片(20 mg)后的血药浓度,并评价两种制剂的生物等效性。方法18名健康男性志愿者分别单剂量口服受试制剂和参比制剂20 mg,采用HPLC-MS法测定血浆中雷贝拉唑的浓度。计算主要药动学参数及相对生物利用度,以判断生物等效性。结果受试制剂和参比制剂在受试者体内的药动学参数:tmax分别为(2.6±0.4)和(2.6±0.3)h,ρmax分别为(684.8±114.1)和(692.4±89.0)μg.L-1,t1/2分别为(1.7±0.5)和(1.8±0.5)h;用梯形法计算,AUC0→t分别为(2 036±358.6)和(2 194±340.3)μg.h.L-1,AUC0→∞分别为(2 169±430.2)和(2 287±348.5)μg.h.L-1;以AUC0→t计算,雷贝拉唑的相对生物利用度平均为(93.1±14.6)%。结论两种雷贝拉唑片具有生物等效性。     

左氧氟沙星分散片在健康志愿者体内的生物等效性评价

目的评价乳酸左氧氟沙星分散片在健康人体内的生物等效性.方法健康男性志愿者共20例随机分为两组,分别单次交叉口服乳酸左氧氟沙星分散片的试验制剂及参比制剂200 mg.采用HPLC法测定血药浓度,计算药动学参数及相对生物利用度,并计算两种制剂的生物等效性.结果受试者口服左氧氟沙星试验制剂或参比制剂的药动学参数t1/2β分别为(6.89±2.11)和(6.62±1.55)h;Tmax分别为(0.74±0.30)和(1.11±0.59)h;Cmax分别为(2.83 ±0.75)和(2.46±0.73)mg·L-1;AUC0～24h分别为(15.64±3.54)和(15.19±3.43)mg·L～·h;AUC0～∞分别为(17.15±4.34)和(16.75±4.29)mg·L-1·h.试验制剂对于参比制剂的平均相对生物利用度以AUC0～24h舢计算为(104.20 ±16.01)％,以AUC0～∞计算为(104.25 ±18.83)％.两种制剂的AUC0～24hAUC0～∞及max经对数转换后双单侧t检验,结果两种制剂生物等效.受试者均未发生药物不良反应.结论左氧氟沙星两种制剂生物等效.     

盐酸氨溴索口崩片与普通片人体生物等效性比较

目的:对国产盐酸氨溴索口腔崩解片和进口普通片进行生物等效性研究。方法:20名健康男性志愿者按2×2交叉试验方案设计,分别口服受试制剂和参比制剂各90mg,并采集服药后24h内动态血标本;采用HPLC-MS/MS法测定血浆中氨溴索质量浓度,计算药动学参数,并判定两种制剂是否生物等效。结果:受试制剂和参比制剂的主要药动学参数Cmax分别为(175.6±57.3)μg.L-1和(173.6±50.7)μg.L-1,tmax分别为(1.3±0.3)h和(1.3±0.4)h,AUC0-24分别为(772.1±275.3)μg.L-1.h和(760.3±205.7)μg.L-1.h,AUC0-∞分别为(862.5±300.8)μg.L-1.h和(839.9±241.5)μg.L-1.h,t1/2(ke)分别为(6.8±2.6)和(6.5±2.9)h,两制剂主要药动学参数经对数转换后进行方差分析及双单侧t检验,并计算90%置信区间,表明两种制剂生物等效,受试制剂的人体生物利用度为(100.3±16.5)%。结论:两种制剂生物等效。     

加替沙星分散片的人体药动学及生物等效性研究

目的 研究加替沙星分散片的人体药动学和生物等效性.方法 健康志愿者20名,随机双交叉单剂量口服加替沙星分散片(试验制剂)和加替沙星片(参比制剂),剂量分别为400 mg,剂间间隔为1周.分别于服药后24 h内多点抽取静脉血;用高效液相色谱法(HPLC)测定血浆中加替沙星的浓度.用DAS药动学程序计算相对生物利用度并评价两种制剂生物等效性.AUC(0-24),UC(0-inf)和Cmax经方差分析和双单侧t检验,max进行秩和检验.结果 单剂量口服试验和参比制剂后血浆中的加替沙星的Cmax分别为(3.75±0.74)mg·L-1和(3.88±0.77)mg·L-1;Tmax分别为(0.81±0.31)h和(1.31±0.55)h;AUC(0-24)分别为(18.48±3.69)mg·h·L-1和(18.45±2.67)mg·h·L-1;AUC(0-inf)分别为(19.24±3.64)mg·h·L-1和(19.20±2.66)mg·h·L-1.AUC(0-24)、AUC(0-inf)和Cmax的90%可信区间分别为91.8%～107.2%、92.1%～107.2%和90.4%～103.0%.结论 试验与参比制剂的人体相对生物利用度为(101.01±19.26)%,两制剂具有生物学等效性.     

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.     

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.     

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.