国产舒芬太尼单剂量给药在心脏手术患者的药代动力学

目的研究国产舒芬太尼(阿片受体激动剂)单剂量给药在心脏手术患者的药代动力学特征。方法随机选择NYHAⅡ～Ⅲ级的成年心脏手术患者8例,麻醉后,经前臂静脉一次性静脉注射国产舒芬太尼5μg.kg-1;采集给药后1,3,5,10,20,30,60,120,240,360 min血标本,-40℃低温保存直至分析。用液相色谱-质谱联用法测定血浆舒芬太尼浓度,3P97药理学程序计算药代动力学参数。结果舒芬太尼血药浓度-时间衰减曲线的三指数函数方程表示为Cp(t)=14.77e-0.518t+3.78e-0.048t+0.32e-0.004t。主要药代动力学参数:t1/2π=(0.03±0.02)h,t1/2α=(0.25±0.07)h,t1/2β=(3.68±2.44)h,Vc=(0.29±0.09)L.kg-1,Vd=(8.24±5.07)L.kg-1,CL=(0.03±0.00)L.(kg.h)-1。结论国产舒芬太尼在心脏手术患者的药代动力学符合三室模型,体外循环可影响其药代动力学特征。     

舒芬太尼在心脏瓣膜置换术患者的药代动力学

目的 研究舒芬太尼(麻醉药)于体外循环下二尖瓣置换术(MVR)患者的药代动力学.方法 随机选择NYHA Ⅱ～Ⅲ级的MVR患者8例,麻醉后前臂静脉注射舒芬太尼5 μg·kg-1.在静脉注射舒芬太尼前和注射后1,3,5,10,20,30,60,120,180,240和360 min,采肝素抗凝血浆1 mL置入密封真空试管中,-80℃低温保存至分析.用液相色谱-质谱联用法测定血浆舒芬太尼浓度,3P97药理学程序计算药代动力学参数.结果 舒芬太尼在MVR患者的药代动力学符合三室开放模型,药物浓度与时间曲线可用三指数函数方程表示.主要药代动力学参数t1/2π=(1.39±0.36) min,t1/2 α=(14.03±4.46) min,t1/2 β=(410.34+41.33) min,Vc=(0.18±0.05) L·kg-1,Vd=(12.01±2.99) L·kg-1,CL=(0.02±4×10-3) L·kg-1·min-1和AUC=(253.85±55.76) ng·mL-1·min.结论 舒芬太尼在MVR患者药代动力学符合三室开放模型,体外循环与血液稀释及患者的心功能状态将影响其药代动力学特征.     

瑞芬太尼在老年和成年外科手术患者的药代动力学比较

目的研究瑞芬太尼在全麻老年患者和成年患者中的药代动力学特征,并进行比较。方法8名老年组和8名成年组外科手术患者静脉给予瑞芬太尼5μg.kg-1,不同时间取血并处理血样,用HPLC/MS/MS方法测定全血中瑞芬太尼浓度;用3P97程序进行药代动力学数据处理,并比较2组的异同。结果静脉注射瑞芬太尼的血药浓度-时间曲线符合二房室模型,老年组和成年组主要的药代动力学参数分别为:t1/2β=(22.32±4.13),(21.28±11.52)min;CL=(2.68±1.12),(2.19±0.35)L.min-1;AUC=(142.69±54.93),(189.83±37.34)ng.min.mL-1。结论老年组和成年组的药代动力学参数几乎没有显著性差异,老年患者临床麻醉给药时无需调整给药方案。     

舒芬太尼在脱泵冠脉搭桥患者与先天性心脏病手术患者的药代动力学比较

目的 比较舒芬太尼(麻醉及术后镇痛药)在脱泵冠脉搭桥(OPCABG)与非紫绀先天性心脏病(NCHD)患者的药代动力学特征.方法 随机选择NYHA Ⅱ～Ⅲ级的心脏手术患者16例.按手术类型分为OPCABG(对照组)和NCHD组2组,每组8例.前臂一次性静脉注射舒芬太尼5 μg·kg-1.在静脉注射舒芬太尼前和注射后1,3,5,10,20,30,60,120,180,240和360 min,采肝素抗凝血浆1 mL置入密封真空试管中,-80℃低温保存直至分析.用液相色谱-质谱联用法测定血浆舒芬太尼浓度,3P97药理学程序计算药代动力学参数.结果 舒芬太尼在心脏手术患者血药浓度与时间曲线可用三指数函数方程表示,在分布项2组的t1/2π和t1/2α均无统计学意义(P＞0.05);t1/2β,Vd,CL和AUC 2组间差异有统计学意义(P＜0.01).结论 舒芬太尼在OPCABG和NCHD患者的药代动力学均可用三室开放模型描述,体外循环与血液稀释、心内分流性疾病和患者心功能状态将影响其药代动力学特征.     

国产舒芬太尼在先天性心脏病与风湿性瓣膜病患者药代动力学比较

目的研究国产舒芬太尼在先天性心脏病(CHD)与风湿性瓣膜病(RHD)手术患者的药代动力学,并进行比较。方法随机选择择期CHD与RHD手术患者16例,分为CHD组和RHD组2组,各8例。静脉注射舒芬太尼5μg.kg-1,用液相色谱-质谱联用法测定血浆舒芬太尼浓度,3P97药理学程序计算药代动力学参数。结果舒芬太尼的药代动力学符合开放的三室模型,其三指数函数在CHD组和RHD组分别为Cp(t)=12.79e-0.4571t+3.3295e-0.0462t+0.3999e-0.0048t和Cp(t)=24.84e-0.5260t+5.3774e-0.0523t+0.1602e-0.0017t。2组间药代动力学参数均有显著性差异(P<0.05)。RHD患者Vd、t1/2β和AUC分别是CHD组的2,2.8,1.4倍,而CHD组的Vc是RHD组Vc的1.8倍(P<0.05)。结论舒芬太尼CHD与RHD患者的药代动力学均符合三室模型,所患疾病与手术类型可影响舒芬太尼的药代动力学特征。     

先心病患者体外循环对舒芬太尼药代动力学的影响

目的研究先心病心内矫治术患者低温体外循环对舒芬太尼药代动力学的影响。方法随机选择NYHAⅡ～Ⅲ级的先心病手术患者16例,分为先心病普通手术组(n=7)和体外循环下先心病矫治手术组(n=9)。入室后建立前臂静脉通路,麻醉后一次性静脉注射舒芬太尼5μg.kg-1。在静脉注射舒芬太尼后1,3,5,10,20,30,60,120,240,360 min采肝素抗凝血浆1 mL。用液相色谱-质谱联用法测定血药浓度,3P97药理学程序计算药代动力学参数。结果 2组患者药代动力学可用三室模型完整描述,其三指数函数方程分别为:Cp(t)=16.6e-1.786t+6.6e-0.171t+0.23e-0.025t和Cp(t)=12.8e-0.457t+3.3e-0.046t+0.4e-0.0048t,2组的t1/2π,t1/2α,t1/2β,Vc,Vd,CL和AUC差异有统计学意义(P<0.01或P<0.05)。结论舒芬太尼在先心病患者药代动力学可用三室模型描述,低温体外循环血液稀释可影响其药代动力学特征。     

老年与青壮年瑞芬太尼药代动力学差异比较

目的探讨老年与青壮年手术患者瑞芬太尼药代动力学参数差异。方法 ASAⅠ或Ⅱ级择期全麻老年及青壮年患者各8例,老年患者年龄62～81岁,青壮年患者年龄18～60岁,全麻诱导时静脉注射瑞芬太尼5μg/kg,于瑞芬太尼注射后1、2、3、5、7、10、15、20、25、30、45、60min分别采集动脉血1.0ml。采用液-液萃取毛细管气相色谱质谱法测定瑞芬太尼血药浓度。结果老年及青壮年患者主要药代动力学参数分别为：t1/2β：（20±9）min、（12±7）min,表现分布容积：（56±17）L、（44±10）L,血浆清除率：（2.7±0.4）L/min、（4.0±0.5）L/min。结论老年与青壮年患者瑞芬太尼药代动力学均符合二房室模型,消除半衰期、表观分布容积、清除率二者明显不同,提示老年与青壮年患者间瑞芬太尼群体药代动力学可能存在差异。     

液-质联用法测定瑞芬太尼在手术患者的全血浓度及其药代动力学

目的建立瑞芬太尼(麻醉药)在手术患者全血体内药物浓度的HPLC/MS/MS测定方法,并进行药代动力学研究。方法10名外科手术受试者静脉给予瑞芬太尼3~6μg·kg-1,用液质联用法测定全血中瑞芬太尼浓度,用3P87程序进行药代动力学数据处理。结果所建立瑞芬太尼全血药物浓度测定方法,回收率和精密度符合要求,符合二房室模型,其主要的药代动力学参数:Cmax=(32.57±7.38)ng·mL-1;t1/2β=(22.07±10.30)min;CL=(30.84±8.15)mL·(kg·min)-1;AUC=(192.80±35.72)ng·min·mL-1。结论测定方法简单、灵敏、准确,适于瑞芬太尼的药代动力学研究。     

多沙普仑在中国朝鲜族和汉族健康人体的药代动力学

目的 研究盐酸多沙普仑注射液(呼吸兴奋药)在中国朝鲜族和汉族健康人体的药代动力学.方法 10名朝鲜族和10名汉族健康受试者,单剂量静脉滴注盐酸多沙普仑注射液50 mg,用高效液相色谱法测定血浆中多沙普仑的浓度,用DAS 2.0药代动力学程序计算药代动力学参数.结果 盐酸多沙普仑注射液在朝鲜族和汉族健康受试者的主要药代动力学参数:Cmax分别为(1.31±0.47),(1.55±0.52)mg·L-1;t1/2分别为(0.39±0.27),(0.33±0.24)h;t1/2β 分别为(4.06±3.06),(3.87±2.17)h;Vc分别为(0.34±0.15),(0.35±0.20)L·kg-1;Vd分别为(1.52±1.19),(1.35±0.96)L·kg-1;CL分别为(0.27±0·07),(0.25±0.11)L·h-1·Kg-1;AUC0-12.5分别为(2.64±0.46),(3.51±1.26)Mg·h·L-1;AUC0-∞分别为(3.01±0.63),(4.06±1.44)mg·h·L-1.结论 朝鲜族和汉族健康受试者单剂量静脉滴注多沙普仑药代动力学参数的差异无统计学意义.     

注射用比伐卢定在中国健康受试者中的药代动力学

目的 研究注射用比伐卢定(抗凝药)在中国健康受试者中的药代动力学.方法 48名健康志愿者接受3种不同剂量的单次静脉推注以及序贯(推注后静滴维持剂量)注射用比伐卢定后,用液相色谱质谱-联用法测定其血药浓度,用WinNonlin 5.2.1进行药代动力学参数计算.结果 单次静脉推注0.50,0.75,1.05 mg·kg-1剂量组的主要药代动力学参数如下:C0分别为(4.90±4.56),(6.50±4.66),(6.81±4.13)mg·L-1;t1/2分别为(0.41±0.12),(0.48±0.17),(0.46±0.15)h;AUC0-t分别为(1.13±0.35),(1.97±0.36),(2.29±0.90)h·mg·L-1.序贯组t1/2为(0.94±0.26)h;AUC0-t为(18.03±6.25)h·mg·L-1.结论 中国健康受试者单次静脉推注比伐卢定0.50～1.05 mg·kg-1,药代动力学呈线性动力学特点,在本剂量范围内,能维持较为恒定的血药浓度.     

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.     

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.     

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.