家兔静注蝮蛇抗栓酶的药物动力学

以家兔凝血时间的延长作为分级定量的药理指标,测定了蝮蛇抗栓酶 iv 给药的药动学参数和 ig给药的生物利用度。按二室开放模型拟合的结果如下:t_(1/2α)=1.12h;t_(1/2β)=3.8h;k_(12)=0.039h~(-1);k_(21)=0.56h~(-1);k_(10)=0.21h~(-1);CL=0.021kg/kg·h;V_c=0.098kg/kg;V_p=0.0069kg/kg;V_(ss)=0.105kg/kg;F=10.9%。     

国产依诺沙星在健康人体内的药代动力学和制剂生物利用度研究

本文报道18例健康志愿者口服依诺沙星后的药代动力学参数和制剂的生物利用度。用高效液相色谱仪测定服药后15小时内的血浆药浓,结果表明:该药吸收迅速、分布相短暂,体内过程符合线性动力学。口服原粉(553mg)后主要药代动力学参数为:t_(max)=1.10±0.49h;C_(max)=4.37±0.82mg/L;K_α=2.89±1.10h~(-1);tlag=0.18±0.08h;AUC_(-noit)=31.71±6.84h·mg/L;其中13例为二室模型:K_(12)=0.51±0.36h~(-1);K_(21)=0.46±0.12h_(-1);t_(1/2)α=0.72±0.27h;t_(1/2)β=6.77±1.12h;另5例为一室模型:t_(1/2)Ke=4.98±0.55h。随机交叉口服片剂(600mg)和胶囊剂(1200mg),未发现血药浓度消除呈现剂量依赖性。供试3种片剂和1种胶囊剂与原粉比较,均具有较高的相对生物利用度,其范围为98.3％～101. 6％。     

盐酸川芎嗪静脉注射的药物动力学研究

大鼠按30mg/kg静脉注射盐酸川芎嗪,体内药物动力学呈开放性二室模型。将每组所得数据的均数按Marquardt法迭代拟合,多项指标帮助选择最佳模型。模型分析得其参数为:t_(1/2α)=0.144lh,t_(1/2α)=1.6953h,K_(21)=2.2850h~(-1),K_(10)=0.8605h~(-1),K_(12)=2.0723h~(-1),AUC=83.3660mg·L·h,CL=0.3597L·kg·h~(-1),V_c=0.4182L·kg~(-1),V_(ss)=0.7975L·kg~(-1).分析结果表明:川芎嗪主要分布于血流丰富的大循环和组织,肾脏排泄少,肝脏为主要消除器官。     

正常人静滴甲硝唑的药代动力学研究

本文以高效液相色谱法对8名健康受试者进行了体内甲硝唑药代动力学初步研究。静脉滴注后的药—时曲线符合开放型双室模型,t_(1/2)α与t_(1/2)β值分别为1.686±1.517与11.995±2.605h;k_(10)、k_(12)及k_(21)分别为0.097±0.056h~(-1)、0.609±0.817h~(-1)及0.748±0.701h~(-1);V_1及V_2分别为0.6±0.2及0.231±0.142L/kg。     

体内药物累积法研究白血康的表观药物动力学

采用体内药物累积法测定小鼠 ip 白血康后的体内过程和药动学参数,白血康在小鼠体内的过程符合二室开放模型,模型方程为:体存率%=87.1711e~(-1.0952t) 138.1771e~(-0.0272t),t_(1/2)α=0.6328h,t_1/2β=25.48h,k_(21):0.6821h~(-1),k_(12)=0.3966h~(-1),k_(10)=0.0437h~(-1),Vc=3.55L/kg.     

高压液相法测定家兔用吡喹酮后的血药浓度及药代动力学参数

本文报道用高压液相法测定家兔用吡喹酮后的血药浓度及药代动力学参数。方法条件:青岛硅胶(5～10μm)柱作吸附层析;正丁醇—氯仿—乙酸乙酯—10％氨水(20:20:60:3)作流动相。荧光检测:λ_(ex)260nm,λ_(em)285nm。检测限为20ng吡喹酮,线性范围为0.1～0.9μg/ml血浆。家兔静注吡喹酮后K_α=3.00h~(-1),t_(1/2(α)=0.23h,K_(el)=0.28h~(-1),t_(1/2(β))=2.48h。家兔口服吡喹酮片剂及胶囊后,胶囊的相对生物利用度为片剂的74.8％。     

用小鼠急性死亡率法测定山莨菪碱的表观药动学参数

用小白鼠急性死亡率法测定了山莨菪碱ip时的经时过程和药动学参数。山莨菪碱在小鼠体内的经时过程为二室开放模型,1.5h之前为分布相,1.5h之后为消除相。用最小二乘法和残余量法求得α、β、A和B四项表现动力学参数分别为3.608h~(-1),0.238h~(-1),529mg/kg(200.2％)和 95mg/kg(35.9％);按药动学公式分别求得分布相表观半寿期(t_(1/2)α)和消除相表现半寿期(t_(1/2)β)为0.2h和2.9h,表观转运速率常数k_(12),k_(21)和k_(10)分别为1.952h~(-1),0.749h~(-1)和1.144h~(-1);表观曲线下面积(AUC)是546mg.h/kg;表观清除率(CI)是0.48kg/(kg.h),表观分布容积V_c,V_p,V_t,和V_b分别为0.42kg/kg,1.10kg/kg,1.53kg/kg和2.04kg/kg.     

一阶导数紫外分光光度法测定氟脲嘧啶的血药浓度及动力学参数

本实验选用一阶导数紫外分光光度法对氟脲嘧啶的血药浓度进行了测定,回收率为100.65%±1.77,CV 1.76%。揭示家兔体内氟脲嘧啶的药物动力学符合一室模型配置。其参数k=1.82±0.32h~(-1),t_(1/2)=0.39±0.07h,Vd=1.56±0.20L/kg。     

锂盐的药代动力学及其临床应用

锂盐是治疗循环性精神躁狂期的有效药物,但其治疗指数窄,容易出现毒性反应。用火焰光度法监测一例病人服药后的血药浓度,拟合了其药代动力学模型为两房室,求出其动力学参数为:α=0.247h~(-1);β=0.0507h~(-1);Ka=2.87h~(-1);t 1/2(β)=13.65h;Vd=0.338L/kg。根据这些参数,制定了合理的用药方案,病人按此方案服药,经多次监测,血药浓度都在有效范围内,真正达到了用药个体化的作用,保证了用药的安全有效。     

硫酸锌在兔体内的药物动力学研究

用原子吸收分光光度法测定兔血清锌、铜浓度。在1.53～15.3μmol/L 范围内为直线,r=0.9996,日内、日间变异系数小于4%,回收率99%,血清中最低检测限为0.122μmol/L。硫酸锌(Zn~(2 ),1mg/kg)静脉注射后,药时曲线符合二室开放模型:α=4.838h~(-1),β=0.320h~(-1),T_(1/2)α=0.149h,T_(1/2)β=2.25h,Vc=0.087L/kg,K_(12)=2.354h~(-1),K_(21)=2.051h~(-1),K_(10)=0.753h~(-1),AUC=34.316h·μg/ml。静注硫酸锌后,兔血清铜浓度降低,提示补锌时应注意对其他微量元素的影响。     

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.     

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.