国产头孢氨苄片与国外同品种的人体生物等效性研究

目的 考察两种（国产与国外同品种）头孢氨苄片的人体生物利用度，评价两制剂在健康人体的生物等效性。方法将20例健康志愿者随机平均分为两组，交叉口服单剂量试验制剂（国产）和参比制剂头孢氨苄片（美国梯瓦制药生产）500 mg,停药清洗期为1周。采用高效液相色谱法测定血浆头孢氨苄浓度。结果单剂量口服试验制剂与参比制剂头孢氨苄片后，两药的主要药动学参数分别为tmax：(0.95±0.40)和（0.99±0.33）h；Cmax：（19.53±5.20）和（19.03±4.39）μg·mL-1；t1/2： (1.03±0.17)和(1.00±0.20) h；AUC0→6h：(33.26±6.60)和(33.39±6.39) μg·h·mL-1；AUC0→∞：(34.05±6.83)和(34.21±6.86) μg·h·mL-1。试验制剂与参比制剂比较,人体相对生物利用度为(99.8±8.0) %。 试验制剂的AUC0→6h和AUC0→∞90%可信区间分别为96.4%～102.6%和 96.5%～102.6%；Cmax的90%可信区间为94.6%～109.4%。两制剂tmax差异无显著性（P＞0.05）。结论单剂量口服试验或参比制剂后，两制剂的主要药代动力学参数Cmax、AUC0→6h、AUC0→∞和tmax均差异无显著性，国产头孢氨苄片与美国梯瓦制药生产的头孢氨苄片具有生物等效性。     

盐酸伐昔洛韦片人体生物等效性研究

目的研究盐酸伐昔洛韦片在健康人体内的生物等效性。方法20名受试者单剂量、交叉口服盐酸伐昔洛韦片受试制剂和参比制剂后,采用高效液相色谱-荧光检测法测定其体内代谢转化物阿昔洛韦的血药浓度,以BAPP2.0程序计算药动学参数和生物等效性数据。结果受试制剂和参比制剂的阿昔洛韦,其Cmax分别为(2.04±0.48)、(1.94±0.37)μg·mL-1,tmax分别为(1.3±0.6)、(1.4±0.6)h,t1/2分别为(2.53±0.42)、(2.55±0.43)h,AUC0～12分别为(5.82±0.99)、(5.54±0.84)μg·h·mL-1,AUC0～∞分别为(6.04±1.04)、(5.76±0.94)μg·h·mL-1。经方差分析和配对t检验,受试制剂与参比制剂的药动学参数无显著性差异(P>0.05),受试制剂的相对生物利用度为(105.7±13.9)%。结论2种制剂具有生物等效性。     

加替沙星分散片的药动学与生物等效性

［摘要］目的研究加替沙星分散片（试验制剂）的人体相对生物利用度和生物等效性。方法用高效液相色谱（HPLC）法测定18例男性健康志愿者交叉口服加替沙星400 mg普通片（参比制剂）和分散片后的血药浓度，求算药动学参数并进行统计学评价。结果单剂量口服试验制剂和参比制剂后血浆中的加替沙星Cmax分别为（3.706±0.768）和（3.912±0.984） μg·mL 1；tmax分别为（0.806±0.349）和（1.306±0.598） h；浓度 时间曲线下面积［AUC(0 24)］分别为（17.721±4.030）和（18.064±3.129） μg·h·mL 1；AUC(0 inf)分别为（18.295±3.943）和（18.695±3.283） μg·h·mL 1；相对生物利用度为（99.62±21.62）%。结论加替沙星分散片与普通片具有生物学等效性。     

盐酸伐昔洛韦片的人体药动学及生物等效性研究

目的:研究单剂量口服盐酸伐昔洛韦片的药动学特征,并评价2种制剂的生物等效性。方法:采用双周期交叉试验方法,18名健康志愿者分别单剂量口服2种盐酸伐昔洛韦片600mg,采用高效液相色谱法测定血浆中药物浓度,计算药动学参数,并进行统计分析。结果:盐酸伐昔洛韦片受试制剂与参比制剂的主要药动学参数tmax分别为(1.69±0.25)、(1.72±0.26)h,Cmax分别为(3.34±0.58)、(3.40±0.49)μg·mL-1,t1/2分别为(2.73±0.31)、(2.97±0.33)h,AUC0～14分别为(11.22±2.21)、(11.12±1.90)μg·h·mL-1,AUC0～∞分别为(11.76±2.15)、(11.61±1.86)μg·h·mL-1。受试制剂相对于参比制剂的生物利用度为(101.06±11.72)%。结论:2种制剂具有生物等效性。     

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。     

米格列醇片在健康人体药动学与相对生物利用度

目的研究健康受试者口服米格列醇片的药动学和相对生物利用度。方法将18例健康受试者随机分组,先后分别服用米格列醇受试和参比制剂各50 mg,用HPLC MS/MS法测定血浆米格列醇浓度。结果主要药动学参数,试验与参比制剂中米格列醇的达峰时间tmax分别为（2.42±0.39）,（2.33±0.34） h;Cmax分别为（0.66±0.22）,（0.66±0.21） μg·mL 1;t1/2分别为（1.96±0.46）,（1.90±0.41） h;AUC0 12分别为（2.86±0.79）,（2.95±0.86） μg·h·mL 1。试验制剂的相对生物利用度为（103.44±11.60）%。 结论试验制剂与参比制剂生物等效。     

盐酸左氧氟沙星胶囊的生物等效性研究

［摘要］目的研究盐酸左氧氟沙星胶囊的人体生物等效性。方法健康志愿者20例,随机双交叉单剂量口服盐酸左氧氟沙星胶囊受试和参比制剂,分别于服药后24 h内多点抽取静脉血,采用反相高效液相色谱（RP HPLC）法测定血浆左氧氟沙星浓度,计算其药动学参数和相对生物利用度,评价其生物等效性。 结果单剂量口服受试和参比制剂后血浆左氧氟沙星峰浓度（Cmax）分别为（3.05±0.64）和（3.25±0.82） μg •mL 1;达峰时间（tmax）分别为（1.00±0.30）和（1.10±0.50） h, 半衰期（t1/2）分别为（7.51±1.26）和（7.45±1.30） h,血药浓度 时间曲线下面积（AUC0～t）分别为（17.58±3.25）和（18.21±2.96） μg•h•mL 1;AUC（0 ∞）分别为（19.04±3.35）和（18.96±3.12） μg•h•mL 1。受试制剂AUC0～t的90%置信区间为参比制剂相应参数的90.9%～102.5%;Cmax的90%置信区间为参比制剂相应参数的84.7%～105.4%。结论盐酸左氧氟沙星受试制剂与参比制剂的人体相对生物利用度为（98.5±16.3）%,受试制剂与参比制剂具有生物等效性。     

左氧氟沙星片剂的人体生物等效性研究

目的评价不同厂家左氧氟沙星片剂的相对生物利用度和生物等效性。方法18名男性健康受试者随机、自身对照交叉单剂量口服不同厂家的左氧氟沙星片剂,采用荧光检测器RP-HPLC法测定血浆中左氧氟沙星质量浓度。结果单剂量口服左氧氟沙星200mg受试和参比制剂的达峰时间tmax分别为(0.99±0·31)和(1.01±0.57)h;血药浓度峰值Cmax分别为(1·73±0·50)和(1·68±0·39)μg·mL-1;t1/2β分别为(6.99±1.00)和(6.71±1.10)h;MRT分别为(9.62±1.58)和(9.44±1.47)h;药时曲线下面积AUC(0→24)分别为(12·46±1·69)和(12·05±1·75)μg·h·mL-1。两种片剂的药物动力学参数均无显著性差异(P>0.05),受试制剂的相对生物利用度(F)为103.80%。结论两种制剂生物等效。     

2种奥美拉唑肠溶胶囊的人体生物等效性研究

目的研究2种奥美拉唑肠溶胶囊的生物等效性。方法20名健康男性志愿者随机分成2组,交叉口服受试制剂和参比制剂各40mg,采用高效液相色谱法测定人血清中奥美拉唑浓度,由DAS软件计算药动学参数及相对生物利用度。结果受试制剂与参比制剂的t1/2分别为(1.685±0.866)、(1.653±0.862)h,tmax分别为(2.425±0.693)、(2.200±0.865)h,Cmax分别为(0.894±0.481)、(0.865±0.342)μg·mL-1,AUC0～10分别为(2.041±1.446)、(2.022±1.322)μg·h·mL-1,AUC0～∞分别为(2.163±1.594)、(2.125±1.507)μg·h·mL-1,受试制剂的相对生物利用度为(100.3±17.4)%。结论2种奥美拉唑肠溶胶囊具有生物等效性。     

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.