替硝唑对兔体内茶碱药物动力学的影响

采用荧光偏振免疫法（ＦＰＩＡ）测定了单用氨茶碱和氨茶碱与替硝唑合用时兔体内血清茶碱浓度，观察了替硝唑对茶碱药物动力学的影响。结果显示，替硝唑与氨茶碱合并用药时，对茶碱在兔体内的药物动力学参数除使Ｋ２１略升高外均无显著影响，表明替硝唑对氨茶碱的体内过程无影响     

替硝唑对兔体内茶碱动物动力学的影响

采用荧光偏振免疫法（ＦＰＩＡ）测定了单用氨茶碱和氨茶碱与替硝唑合用时兔体内血清茶碱浓度，观察了替硝唑对茶碱药物动力学的影响。结果显示，替硝唑与氨茶碱合并用药时，对茶碱在兔体内的药物动力学参数除使Ｋ２１略升高外均无显著影响，表明替硝唑对氨茶碱的体内过程无影响。     

剂量-依赖性药物动力学与癌症的化学治疗

大多数药物的体内消除过程遵循一级动力学规律,在治疗剂量范围内描述药物消除的动力学参数不变。为数不多的药物显示剂量-依赖性药物动力学(亦称非线性药物动力学),其动力学参数依赖所用药物的剂量。某些情况下,单剂药物在消除期间的动力学参数随体内药物浓度而变化。剂量-依赖性药物动力学的类型产生剂量-依赖性药物动力学的主要原因     

氨氯地平对家兔体内茶碱血药浓度及药物动力学参数的影响

目的：观察氨氯地平对茶碱血药浓度及药物动力学参数的影响。方法：采用荧光偏振免疫分析法（FPIA）测定氨茶碱单用及与氨氯地平合用后家兔体内茶碱血清浓度。并对2组药物动力学参数进行统计学处理。结果：单用氨茶碱及与氯氯地平合用后的药－时曲线符合一定模型。氨氯地平对茶碱的血药浓度及药物动力学参数均无显著影响。结论：家兔体内氨氯地平与氨茶碱可以联合应用，无需调整氨茶碱的剂量。     

高效液相色谱法在体内药物分析中的应用

用高效液相色谱法测定体液内药物及其代谢产物，可为药物代谢动力学，临床药理学和毒理学等研究提供科学依据。体内药物分析最常用的体液是比较容易得到的血样（血浆、血清、全血）、尿样、唾液及组织液，特殊情况下也采用乳汁、泪液、胆汁、羊水、粪便等接近有关药物作用点的检体[1]。一、血样中的药物浓度测定血浆和血清是体内药物分析最常采用的样本，选用最多的是血浆，因为当药物在体内达到稳定状态时，血浆中药物浓度被认为是与药物在作用点的浓度密切相关，即血浆中的药浓可以反映药物在体内的状况[2]。Marten等卜］主张用（＞I3S…     

氢化与非氢化卵磷脂对阿霉素脂质体体内外稳定性的影响

目的研究卵磷脂(EPC)和氢化卵磷脂(HEPC)对阿霉素脂质体的体外泄漏及体内循环时间的影响.方法用透析法考察EPC及HEPC普通脂质体在37℃小牛血清及37℃,20℃和4℃PBS中的药物泄漏情况;用高效液相色谱法研究了EPC和HEPC长循环脂质体在大鼠体内的药物动力学.结果在37℃小牛血清中HEPC脂质体较EPC脂质体泄漏慢,而在PBS中则结果相反;大鼠体内药物动力学研究结果表明,HEPC长循环脂质体在血中的平均驻留时间(MRT)较EPC长循环脂质体长得多(23.3h vs 12.0h).结论HEPC长循环脂质体是靶向血管外部位的更好的药物载体.     

十一酸睾酮自微乳制剂的大鼠体内药代动力学研究

目的制备十一酸睾酮自微乳化制剂,并对其大鼠体内药代动力学进行研究。方法采用血清睾酮放免法测定给药后大鼠体内血清睾酮水平的变化,并计算药代动力学参数。结果十一酸睾酮原料药混悬液基本没吸收,而自微乳制剂和市售Andriol药物的吸收大大提高。以Andriol为参比制剂,自微乳制剂的相对生物利用度为96.4%。结论自微乳化给药系统能提高脂溶性药物十一酸睾酮的吸收。     

稳态表观分布容积

表观分布容积是一个有用的药物动力学参数,它把血浆或血清的药物浓度与体内药物总量联系起来,即药物分布在相等于具有血浆中浓度时所占体液的体积。一般地可以说表观分布容积(V_d)=体内药量(X_B)/对应的血浆中药物浓度(C) (1) 为什么说表观,因为它并不代表有生理意义的真正容积。而它的比值是时间的函数。由于分配容积大小可推测药物在体内分布及结合情况,故它有广泛的实用意义。(V_d)值     

癫痫患者血清、血清超滤液、唾液、脑脊液中苯妥英浓度的相关性和动力学研究

本文应用超滤法测定血清中游离苯妥英浓度的方法,并采用荧光酶免疫法对患者的血清、血清超滤液、唾液、脑脊液进行苯妥英浓度测定,研究它们的相关性。通过测定6名癫痫患者单剂量口服苯妥英钠后血清、血清超滤液、唾液中的药物浓度,计算其动力学参数。实验结果表明,血清超滤液、唾液、脑脊液中苯妥英浓度分别为血清药物浓度的11%、10%、11%,有良好的相关性。各样品测得的动力学数据基本一致,药物浓度—时间曲线变化相同。血清超滤液、唾液、脑脊液样品中苯妥英浓度均反映了患者体内游离药物浓度的情况,唾液样品收集方便、迅速,对患者无损伤,适用于临床进行治疗药物监测。     

建国以来中草药有效成分的药物代谢动力学研究

药物代谢是研究药物的体内过程—吸收、分布、结构转化和排泄。药物代谢动力学(简称药代动力学)是用数学模式定量研究药物体内过程的动态变化。药物体内过程及其动力学研究对于指导临床合理用药有特殊重要的意义。本文评述了建国35年来中草药有效成分、包括其合成品和衍生物或有效部位的体内过程及药代动力学研究的情况,并试图对研究前景作一展望。     

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.