瑞舒伐他汀钙胶囊和片剂在健康人体内药动学和生物等效性研究

目的:研究瑞舒伐他汀钙胶囊和片剂在健康人体内的药动学过程和相对生物利用度。方法:健康志愿者24名,随机双交叉单剂量口服瑞舒伐他汀钙胶囊(受试制剂)和瑞舒伐他汀钙片(参比制剂),剂量均为20 mg,采用HPLC-MS/MS测定血浆中瑞舒伐他汀钙的浓度,用DAS 3.0药动学程序计算药动学参数和生物利用度,并进行生物等效性评价。结果:单剂量口服瑞舒伐他汀钙受试和参比制剂后,血浆瑞舒伐他汀的tmax分别为(3.56±1.68)h和(3.63±1.56)h;Cmax分别为(21.17±13.74)ng·ml-1和(26.33±23.22)ng·ml-1;t1/2分别为(10.68±5.50)h和(9.04±6.00)h;AUC0-t分别为(219.31±146.09)ng·h·ml-1和(252.43±194.96)ng·h·ml-1;AUC0-∞分别为(225.32±146.76)ng·h·ml-1和(257.24±194.61)ng·h·ml-1,AUC0-t、AUC0-∞和Cmax的90%置信区间分别为81.1%~106%,81.8%~105.4%和77.9%~104.5%。受试制剂的相对生物利用度F为(100.7±54.1)%。结论:瑞舒伐他汀钙受试制剂与参比制剂具有生物等效性。     

氯吡格雷二硫酸盐人体生物等效性研究

目的:研究氯吡格雷二硫酸盐受试制剂和参比制剂在20名健康男性志愿者体内的药动学和相对生物利用度,并进行等效性评价。方法:采用双交叉试验法单剂量口服75 mg的两种氯吡格雷二硫酸盐片,采用液相色谱-质谱联用法测定血浆中药物浓度。结果:单剂量口服75 mg受试制剂后,测得t1/2t、maxc、max、AUC0~36、AUC0~∞分别为(6.6±4.9)h、(0.64±0.21)h(、1.72±1.38)ng/ml、(1.99±1.22)ng.h.ml-1、(2.11±1.21)ng.h.ml-1;参比制剂为(6.3±7.0)h、(0.68±0.27)h(、1.75±1.86)ng/ml、(2.11±1.49)ng.h.ml-1(、2.18±1.50)ng.h.ml-1。氯吡格雷二硫酸盐片受试制剂相对生物利用度为(108.5±52.3)%。结论:受试制剂与参比制剂具有生物等效性。     

奥美拉唑肠溶胶囊人体相对生物利用度和生物等效性研究

目的:比较两种奥美拉唑肠溶胶囊的人体相对生物利用度,并做出生物等效性评价,以考察试验制剂的药品质量.方法:按照两制剂两周期随机交叉设计,19名男性健康志愿者单剂量口服试验胶囊(20mg×2)和参比胶囊(40mg).采用HPLC法测定血浆奥美拉唑浓度.运用DAS2.0软件计算药动学参数,并进行统计学分析.结果:单剂量口服40mg的奥美拉唑肠溶试验胶囊和参比胶囊后,AUC0?12分别为(3184.81±2055.44)ng·h·ml-1和(3062.46±1957.74)ng·h·ml-1,AUC0?8分别为(3361.55±2370.29)ng·h·ml-1和(3186.89±2042.69)ng·h·ml-1;Cmax分别为(1066.44±482.99)ng·ml-1和(1072.99±472.30)ng·ml-1;Tmax分别为(2.50±0.82)h和(2.37±0.72)h;受试胶囊对参比胶囊平均相对生物利用度为(107.33±23.44)%.结论:试验胶囊与参比胶囊具生物等效性.     

氯雷他定胶囊在健康人体的生物等效性

目的:评价国产氯雷他定胶囊与进口片剂在健康人体生物等效性。方法:采用双周期自身对照交叉试验设计,20名健康志愿者单次口服40mg供试制剂和参比制剂,采用固相萃取反相HPLC,测定血浆中氯雷他定的浓度。结果:氯雷他定片剂和胶囊的AUC0-∞分别为(57.3±20.7)μg.h.L-1和(60.1±23.7)μg.h.L-1,AUC0-8分别为(56.5±20.8)μg.h.L-1和(59.2±23.8)μg.h.L-1,Cmax分别为(22.9±5.1)μg.h.L-1和(22.9±5.4)μg.L-1,tmax分别为(0.93±0.20)h和(1.06±0.25)h,t1/2分别为(1.3±0.4)h和(1.2±0.4)h,氯雷他定胶囊相对于进口片剂生物利用度为(105.0±12.3)%,经方差分析,双单侧t检验差异均无显著性。结论:氯雷他定胶囊与片剂生物等效。     

氯雷他定口崩片的人体生物等效性研究

目的建立测定人血浆中氯雷他定的高效液相色谱法(HPLC),研究氯雷他定口崩片在男性健康志愿者体内的药动学行为,评价其人体相对生物利用度和生物等效性。方法 18例健康男性志愿者随机分组自身交叉对照实验设计,单剂量口服氯雷他定口崩片受试制剂和参比制剂20mg,HPLC法测定服药后12h内不同时间血浆中氯雷他定的质量浓度,BAPP药动学程序计算相对生物利用度并评价2种制剂的生物等效性。结果受试制剂和参比制剂的主要药动学参数:tmax分别为(0.90±0.30)和(0.80±0.10)h;Cmax为(42.57±7.88)和(42.96±6.97)ng.mL-1;t1/2分别为(2.20±0.35)和(2.07±0.50)h;药时曲线下面积AUC(0→12h)分别为(126.00±23.30)和(123.24±30.55)ng.h.mL-1。受试制剂的相对生物利用度为104.6%±14.7%。结论建立的分析方法准确灵敏,统计学分析表明2种制剂生物等效。     

非那雄胺片的药物动力学和人体相对生物利用度

20名健康男性志愿者交叉口服非那雄胺的受试制剂与参比制剂,采用LC-MS法测定血浆中的非那雄胺.单剂量口服受试或参比制剂10 mg后,Cmax分别为(94.15±18.71)和(99.13±20.10)ng/ml;tmax分别为(2.2±0.7)和(2.4±0.9)h;t1/2分别为(43±0.7)和(4.2±1.1)h;AUC0～24h分别为(614.57±129.11)和(627.65±145.40)ng·h·ml-1;AUC0～∞分别为(631.94±136.97)和(646.20±150.63)ng·h·ml-1;受试制剂的相对生物利用度为(100.2±18.4)%.经方差分析和双单侧t检验,两种片剂具有生物等效性.     

亚叶酸钙片的人体生物利用度及生物等效性研究

目的:研究亚叶酸钙片在健康受试者体内的相对生物利用度和生物等效性.方法:采用两制剂双周期随机交叉试验设计,18名男性健康受试者单剂量口服亚叶酸钙片或参比片剂75mg,用HPLC测定血浆亚叶酸浓度.采用3P97药动学程序进行数据处理.结果:试验片剂与参比片剂的AUC0-24h分别为(4608.68±806.72)ng·ml-1·h和(4868.73±909.83)ng·ml-1·h;Cmax分别为(484.82±72.87)ng·ml-1和(499.50±108.19)ng·ml-1;Tmax分别为(2.33±0.30)h和(2.47±0.27)h.结论:两种制剂主要药动学参数均无显著性差异.与参比片剂相比,试验片剂的相对生物利用度为(96.48±18.60)%,两者具有生物等效性.     

地氯雷他定片在中国健康受试者的生物等效性研究

目的 评价地氯雷他定片仿制药与原研药在中国健康受试者中单剂量空腹和餐后条件下给药的生物等效性。方法 用单中心、随机、开放、单次给药、两制剂、两周期、双交叉试验设计,空腹和餐后试验各入组24例受试者。空腹或餐后条件下单次口服地氯雷他定片受试制剂和参比制剂5 mg,用液相色谱串联质谱法测定血浆中地氯雷他定的浓度。用Phoenix WinNonlin 8.0软件计算主要药代动力学(PK)参数。结果 空腹组的地氯雷他定片受试制剂和参比制剂主要PK参数：地氯雷他定C_max分别为(3.81±1.44)和(3.76±1.25)ng·mL^-1,AUC_0-t分别为(52.18±19.21)和(50.71±18.21)ng·mL^-1·h, AUC_0-∞分别为(54.52±19.71)和(53.19±19.07)ng·mL^-1·h。餐后组的地氯雷他定片受试制剂和参比制剂主要PK参数：地氯雷他定C_max分别为(3.52±1.20)和(3.55±1.10)ng...     

HPLC/MS法研究国产氯雷他定片的人体生物等效性

目的评价国产及进口氯雷他定片的生物等效性。方法用随机交叉试验方法,18名受试者按体重指数进行分层,随机服用氯雷他定片试验制剂或参比制剂。结果试验制剂与参比制剂的tmax分别为1.3±0.2和1.3±0.3h,Cmax分别为:38.47±17.41和39.03±18.33mg.L-1,用梯形法计算所得的AUC0-t分别为:139.19±49.03和144.33±65.66ng.h.mL-1,氯雷他定试验制剂的相对生物利用度为(100.7±13.6)%。结论2制剂具有生物等效性。     

人血浆中胺碘酮分散片的药动学研究

建立TLC-MS法测定人血浆中胺碘酮的浓度,并研究了18名健康受试者随机交叉口服胺碘酮分散片(受试制剂)和胺碘酮片剂(参比制剂)0.4g后的药动学.口服受试和参比制剂后的药动学参数分别为cmax(419.96±211.72)和(414.85±166.66)ng/ml,tmax(4.2±1.2)和(3.8±0.9)h,t1/2(38.8±20.4)和(39.6±12.5)h,AUC0-96h(6375.29±3093.14)和(6518.38±3101.07)ng·h·ml-1,AUC0→∞(7165.29±3680.16)和(7325.51±3478.09)ng·h·ml-1.受试制剂的相对生物利用度为(98.37±8.38)%.双单侧t检验结果表明,两种制剂具有生物等效性.     

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.

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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.     

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.