冰片对不同药物体内药代动力学的影响

冰片作为一种常用中药,可明显改善联用药物的渗透性及分布等.近年来,冰片与其他药物联用成为研究热点,但冰片对其他药物在体内的药代动力学影响研究较少.本文综述了近年冰片对其他药物在体内的药代动力学影响,为相关药物的研发及临床应用提供参考.     

大黄酸对药物转运体和代谢酶影响的研究进展

药物转运体和药物代谢酶是影响药物体内处置过程中至关重要的因素。大黄酸作为传统中药大黄的主要活性成分,具有广泛药理活性。研究发现,大黄酸与药物转运体和代谢酶密切相关,能够直接激活或抑制多种转运体的功能及其蛋白表达。而且大黄酸对药物代谢酶细胞色素P450（CYP450）的功能及其蛋白表达同样有抑制作用。因此,大黄酸与其他药物合用时,可能发生基于药动学的药物相互作用（drug-drug interaction,DDI）。从药物转运体和代谢酶的体内分布、大黄酸对转运体及代谢酶的影响等方面进行综述。     

P-糖蛋白与药物的结合体在体内的转化过程探讨

目的 ATP 结合盒转运载体蛋白作为影响药物体内过程的重要因素已被广泛研究 ,P-糖蛋白(P-gp)是其中最主要的一种转运子.P-gp的结构、特点及组织分布决定了其在药物的吸收、分布、代谢、排泄方面的重要作用.了解 P-gp 的这些作用有助于增加临床用药的合理性.经过近三十年的发展, 虽然研究P-gp的方法已经较为成熟;但是, 目前对转运子的研究仍有许多争议存在, 还有很多问题需要解决.本文主要阐述P- gp 的特性及其对药物体内过程的影响.     

黄柏药效物质基础成分初探

目的:通过黄柏血清药物化学和代谢组学研究,探索黄柏的药效物质基础.方法:利用HPLC对比体外药材图谱、体内血清图谱及尿液图谱,确定黄柏的入血成分及尿液中的代谢成分,综合评价黄柏体内直接作用的物质基础.结果:确定了黄柏给药后16个血中移行成分中的2个成分,尿液代谢物13个成分中8个峰与血中移行成分中的8个峰HPLC图在相同保留时间出峰,光谱类似,其他5个成分可能为代谢产物.结论:对黄柏血中移行成分及代谢产物进行深入研究,可为探讨黄柏药效物质基础提供依据.     

柚皮苷的药物代谢动力学研究概况与进展

柚皮苷是一种二氢黄酮类化合物,具有促进胃肠蠕动功能,主要存在于枳壳、枳实、骨碎补、化橘红等中药中。柚皮苷的口服吸收差,体内分布广泛,主要经开环、脱氢、裂解等反应产生对羟基苯丙酸、对羟基桂皮酸等代谢产物而排出体外。同时柚皮苷还能够通过抑制部分转运体、代谢酶的活性与其他药物发生相互作用,从而影响其他药物的代谢过程。本文通过综述柚皮苷的药物代谢动力学特征及柚皮苷对其他药物的代谢动力学的影响,发现柚皮苷代谢过程的相互作用机制及基因多态性对其药代动力学特征的影响尚需深入研究。     

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。     

基于胃肠动力障碍模型大鼠的气滞胃痛颗粒血清药物化学初步研究

目的 利用血清药物化学研究胃肠动力障碍模型大鼠灌胃气滞胃痛颗粒后的入血成分.方法 采用超高效液相色谱-电喷雾-飞行时间质谱技术,确定胃肠动力障碍大鼠口服气滞胃痛颗粒提取物后血中移行成分及其代谢产物.结果 胃肠动力障碍模型大鼠灌胃给予气滞胃痛颗粒后血清中检测25个移行成分,4个原型入血成分及21个代谢成分,并对其中的18个成分进行了结构推测.结论 血中移行成分及代谢产物可能为气滞胃痛颗粒发挥促胃肠动力的体内直接作用物质,为明确气滞胃痛颗粒药效物质基础提供了科学依据.     

甘草对药物代谢酶以及化学药物体内代谢的影响

甘草对肝细胞色素P450(CYP450)酶活性具有诱导或抑制作用,对一些化学药物如氨茶碱、安替比林、丙米嗪、利多卡因、氯沙坦等的体内代谢产生影响,合用时使这些药物的药物代谢动力学发生改变,在临床应用过程中应注意。因此,需要进一步在人体内研究甘草提取物及其有效成分与其他药物的相互作用。从CYP450酶角度研究中药,有利于从分子水平探讨中药的作用机制或毒性机制,并有可能揭示中药之间或中药与西药产生相互作用的关系,防止临床配伍用药后的不良反应,从而提高中药临床应用的有效性与安全性,促进临床合理用药。本文综述了甘草对药物代谢酶以及化学药物体内代谢的影响。     

体外模型在中药代谢研究中的应用

体内代谢研究对阐明中药药效物质基础及作用机制有重要意义。体外模型由于其替代、简化和精准的特点,已成为中药体内代谢研究的重要手段之一。综述药物体内过程研究中常用的体外模型及其特点,并总结其在中药代谢研究中的应用概况,以期为中药成分代谢研究提供理论和方法学参考。     

药物与肝脏(合理用药讲座)

肝脏是人体内最重要的代谢器官,几乎参与体内的一切代谢过程,故有“物质代谢中枢”之称。绝大多数药物的代谢也在肝脏中进行。近年来临床药学也从事研究药物在人体中从摄入到排出体外,称作研究“药物体内命运”问题,肝脏是“药物体内命运”中重要环节。本文从三个方面谈药物与肝脏的关系。     

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.     

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.