丙戊酸钠缓释片的人体生物等效性研究

目的 评价两种丙戊酸钠缓释片的生物等效性.方法 采用开放,随机交叉试验设计,20名健康男性志愿者单剂量口服丙戊酸钠缓释片参比制剂和受试制剂各1000mg,用高效液相-荧光色谱法测定不同时间血清中丙戊酸钠的浓度并计算其主要的药代动力学参数.结果 单剂量口服两种丙戊酸钠缓释片主要药代动力学参数:Cmax分别为115.34±12.24和109.34±11.84μg·mL-1;tmax分别为0.91±0.74和0.98±0.68h;AUC0-∞分别为1.92±0.58和1.91±0.64mg·h·mL-1;利用方差分析及双单侧t检验对两种丙戊酸钠缓释片的生物等效性进行评价.结论 两种厂家生产的丙戊酸钠缓释片具有生物等效性.     

国产与进口齐多夫定胶囊在健康人体的药代动力学和生物等效性

目的研究国产与进口齐多夫定胶囊(抗艾滋病药)在健康志愿者体内的药代动力学和生物等效性。方法20名健康男性受试者随机交叉单剂量口服国产与进口齐多夫定胶囊300mg,用高效液相色谱法测定给药后不同时间的血浆浓度,计算主要药代动力学参数。结果国产与进口齐多夫定胶囊主要药代动力学参数:t1/2分别为(1.72±0.42),(1.53±0.27)h;tmax分别为(0.86±0.42),(0.88±0.30)h;Cmax分别为(1.60±0.61),(1.60±0.55)μg.mL-1;AUC0～8分别为(2.06±0.37),(2.08±0.34)μg.h.mL-1;AUC0-∞分别为(2.11±0.37),(2.12±0.34)μg.h.mL-1。国产齐多夫定胶囊相对生物利用度F为(99.02±5.02)%。结论2制剂具有生物等效性。     

烟酸缓释片在健康人体的生物等效性

目的 研究烟酸缓释片(广谱凋血脂药)在健康人体的药代动力学,并评价其生物等效性.方法 30名男性健康志愿者随机交叉单剂量口服试验制剂或参比制剂1.5 g,用高效液相色谱-串联质谱法测定血浆中烟酸浓度.结果 单剂量口服烟酸试验制剂或参比制剂1.5 g,药代动力学参数如下:AUC0-t分别为(20.05±16.29),(21.61±18.06)μg·h·mL-1;AUC0-∞分别为(20.81±16.30),(22.81±18.47)μg·h·mL-1;Cmax分别为(8.72±6.81),(9.57±8.22)μg·mL-1;tmax分别为(4.41±1.34),(4.31±1.29)h;t1/2分别为(4.00±4.90),(2.91±3.39)h,烟酸缓释片的相对生物利用度为(96.6±30.9)%.结论 受试制剂与参比制剂生物等效.     

依卡倍特二钠颗粒在健康人体中的单次给药药代动力学研究

目的研究中国健康志愿者单剂量口服2.0、4.0g依卡倍特二钠颗粒后的药代动力学行为,并评价药代动力学参数在2.0～4.0g范围内剂量相关性。方法 10名健康志愿者,随机交叉试验,分别单剂量口服依卡倍特二钠颗粒2.0、4.0g;测定给药后36h内的血药浓度。结果单剂量口服2.0、4.0g依卡倍特二钠颗粒后,依卡倍特的t1/2分别为(11±5)h和(9±4)h,达峰浓度(Cmax)分别为(4 998±982)ng/mL和(11 699±4 143)ng/mL,AUC0～t分别为(43 863±10 341)ng.h-1.mL-1和(92 492±30 915)ng.h-1.mL-1,AUC0～∞分别为(48 611±15 029)ng.h-1.mL-1和(99 628±35 993)ng.h-1.mL-1。结论在2.0～4.0g剂量范围内依卡倍特呈线性药代动力学,Cmax、AUC的升高与剂量成正比。     

国产丙戊酸钠无糖口服液人体生物等效性研究

目的评价国产丙戊酸钠无糖口服液和进口丙戊酸钠糖浆两种制剂的生物等效性.方法20例健康男性志愿者双周期随机交叉口服单剂量1 000mg(25mL)国产丙戊酸钠无糖口服液和进口丙戊酸钠糖浆两种制剂,分别于服药前及服药后0.33,0.67,1,1.5,2,4,8,12,24,36,48及72h采集血样.用高效液相-荧光色谱法测定血清中丙戊酸钠的浓度,并对试验数据进行处理.结果单次口服国产及进口丙戊酸钠制剂的Cmax分别为(112.65±16.91)和(110.22±15.20)μg@mL-1;Tmax分别为(0.86±0.38)和(1.09±0.48)h;AUCo～72h分别为(1 980.24±275.82)和(1 950.11±305.60)μg@h@mL-1;AUC0～∞分别为(2 088.19±313.25)和(2 075.30±367.58)μg@h@mL-1;单次口服国产丙戊酸钠无糖口服液的相对生物利用度F0～72h为(102.96±15.37)%,Fo～∞为(102.25±15.61)%.结论单次口服国产丙戊酸钠无糖口服液和进口丙戊酸钠糖浆具有生物等效性.     

加替沙星片人体药代动力学及生物等效性研究

目的:在中国健康成年男性志愿者中比较研究国产和进口加替沙星片剂的药代动力学参数,评估两者的生物等效性。方法:24名健康男性志愿者随机自身前后交叉给药,分别单剂口服国产和进口加替沙星片400mg。以HPLC测定血药浓度,应用DAS软件计算两者的药代动力学并考察其生物等效性。结果:受试者分别应用国产片剂(试验制剂)和进口片剂(参比制剂)400mg后,两药药-时曲线均符合二房室模型,主要药代动力学参数:Tmax分别为(0.99±0.41)h和(1.11±0.60)h;Cmax分别为(4.11±0.76)μg/mL和(3.89±0.54)μg/mL;t1/2β分别为(7.75±0.81)h和(7.39±0.92)h;AUC0-36h分别为(29.81±5.70)μg·mL-1·h和(30.77±4.40)μg·mL-1·h;AUC0-∞分别为(30.97±6.01)μg·mL-1·h和(31.85±4.58)μg·mL-1·h;国产片剂对于进口片剂的相对生物利用度F0-36h为(97.63±19.15)%。结论:国产与进口加替沙星片剂为生物等效制剂。     

进口与国产比卡鲁胺片在健康人体的生物等效性

目的研究比卡鲁胺片在(抗雄性激素药)在健康人体内的药代动力学,并比较国产与进口2种制剂的生物等效性。方法44名健康男性志愿者随机平行口服单剂量国产(试验制剂)或进口比卡鲁胺片(参比制剂)50mg后,用高效液相色谱法测定血浆中比卡鲁胺片浓度,用DAS软件计算2者的药代动力学参数及相对生物利用度,并评价2种制剂的生物等效性。结果国产和进口比卡鲁胺片的AUC0-n分别为(94.4±20.6)和(102.3±17.4)μg.h.mL-1;AUC0-∞分别为(102.1±20.8)和(108.7±18.9)μg.h.mL-1,Cmax分别为(538±151)和(619±167)ng·mL-1;tmax分别为(21±12)和(23±12)h,生物利用度F=93.9%。结论国产和进口比卡鲁胺片具有生物等效性。     

丙戊酸钠缓释片在犬体内的药代动力学和相对生物利用度研究

目的建立测定犬体内血清丙戊酸钠浓度的HPLC方法,研究丙戊酸钠缓释片在犬体内的药代动力学及其相对生物利用度。方法 采用双周期交叉试验设计,对健康Beagle犬进行单剂量口服丙戊酸钠缓释片和普通片,用柱前衍生高效液相色谱法测定犬体内血清丙戊酸钠浓度,并对两者的药代动力学参数进行比较。结果单次口服丙戊酸钠缓释片及普通片的Cmax分别为27.88±2.73μg/ml和31.53±2.51μg/ml,Tmax分别为6.0±0.37h和2.0±0.21h,t1/2分别为9.81±0.91h和6.40±0.62h,AUC0→∞分别为414.23±43.87μg/h.ml和403.12±41.22μg/h.ml,其相对生物利用度为102.76±5.89%。结论丙戊酸钠缓释片与普通片在Beagle犬体内生物等效。     

氟康唑胶囊在健康人体的药代动力学及生物等效性

目的建立人血浆氟康唑(抗真菌药)HPLC测定法,比较氟康唑2种制剂在健康志愿者体内的药代动力学和相对生物利用度。方法用随机开放交叉试验设计,20名健康志愿者分别单剂量口服试验和参比制剂氟康唑胶囊300mg,用高效液相色谱法法测定血药浓度,计算2制剂的药代动力学参数,并进行生物等效性评价。结果试验和参比制剂氟康唑胶囊的主要药代动力学参数t1/2分别为(31.20±3.98),(31.51±3.26)h;tmax分别为(2.83±0.37),(2.65±0.24)h;Cmax分别为(6.20±1.08),(6.11±1.01)μg·mL-1;AUC0-96分别为(208.42±21.77),(200.27±18.27)μg·h·mL-1;AUC0-∞分别为(234.00±24.56),(227.14±20.91)μg·h·mL-1。各药代动力学参数无显著性差异(P>0.05)。试验制剂氟康唑胶囊相对生物利用度F为(104.3±8.5)%。结论2制剂具有生物等效性。     

美索巴莫胶囊在健康人体的药代动力学及生物等效性

目的研究美索巴莫胶囊(肌松药)在健康人体的药代动力学及其生物等效性。方法按两制剂双周期自身对照交叉试验设计,18名男性健康志愿者分别单剂量口服2种国产美索巴莫胶囊(参比制剂)和(受试制剂),用RP-HPLC法测定血药浓度,计算药代动力学参数,并评价2制剂的生物等效性。结果口服美索巴莫胶囊参比制剂和受试制剂750mg后的主要药代动力学参数:Cmax分别为(13.87±2.44)和(14.34±2.99)μg.mL-1;tmax分别为(0.82±0.21)和(0.80±0.23)h;AUC0-12分别为(32.79±10.03)和(33.90±8.40)μg.h.mL-1;AUC0-∞分别为(33.91±9.89)和(35.00±8.79)μg.mL-1;t1/2Ke分别为(1.91±0.58)和(1.79±0.59)h;美索巴莫的相对生物利用度F0-12平均为(105.0±11.2)%,F0-∞平均为(104.3±10.2)%。结论2种美索巴莫胶囊制剂生物等效。     

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.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

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.