体液中药物浓度测定与免疫分析

一、体液中药物浓度测定的意义测定体液内药物浓度与了解药物在体内代谢过程已是药物分析工作者面临的重要课题。体液中药物浓度测定对临床药物血浓度监测、药物代谢动力学研究与生物利用度测定都是非常重要的。 (一)临床药物血浓度监测有许多药物的治疗指数较低,甚至与中毒剂量很为接近,由于病人代谢、遗传或服其他药物的影响,使一般认为正常的治疗剂量     

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。     

健康人奥硝唑唾液浓度与血浆浓度的相关性考察

目的:研究健康人奥硝唑唾液与血浆浓度的相关性,为临床利用唾液进行奥硝唑治疗药物监测提供依据。方法:12名健康志愿者单剂量口服奥硝唑胶囊1.0g后,采用HPLC法测定奥硝唑的唾液和血浆中的药物浓度,比较两者的相关性。结果:奥硝唑血浆浓度与唾液浓度的回归方程分别为:AP=51 395.7 CP-13 466.4(r=0.999 8);AS=52 583.5CS-25 234.1(r=0.999 2)。奥硝唑唾液浓度与血药浓度回归方程为CS=1.046 CP+0.836,r=0.990(n=156),其比值(S/P)为(0.89±0.06)。结论:奥硝唑在健康志愿者唾液中的药物浓度与血药浓度显著相关,稳定性好,可以应用唾液进行治疗药物监测。     

癫痫患者血清与唾液中卡马西平浓度的相关性研究

目的:研究卡马西平在癫痫患者血清与唾液中药物浓度的相关性,探索用唾液监测卡马西平药物浓度的可行性。方法:采用高效液相色谱法测定卡马西平在癫痫患者血清、血清超滤液和唾液中的浓度,按年龄(分为未成年和成年组)和剂量(分为小剂量和大剂量组)分组后,用SPSS12.0软件对数据进行相关性分析。结果:未成年组与成年组、大剂量组与小剂量组的血清与唾液中卡马西平浓度的相关性系数分别为r未成年=0.492与r成年=0.862、r小剂量=0.572与r大剂量=0.846,血清、血清超滤液与唾液中卡马西平浓度的相关性系数分别为r血清/唾液=0.601、r血清超滤液/唾液=0.806。结论:对于成年组和大剂量组,卡马西平在血清和唾液中浓度呈线性相关(r>0.84),且癫痫患者唾液中的药物浓度与血清中的游离药物浓度相关性更好。因此,本试验为临床上采用唾液法进行卡马西平浓度监测提供了一定的试验依据。     

新抗癫痫药物唾液浓度监测的研究

癫痫是一种慢性反复发作性疾病．需要长期甚至终生服药．而抗癫痫药物（antiepileptic drugs,AEDs）的个体差异较大．尤其是儿童处于生长发育期。剂量的变化是一个动态的过程。多年来,血药浓度监测对临床安全有效地使用抗癫痫药物起了至关重要的作用[11。1974年．Gorodetzky和Kullberg首先提出．用唾液代替血清进行治疗药物监测（Therapeufic Drug Monitoring。TDM）,现已有100余种药品用唾液作为药物浓度监测．包括传统抗癫痫药物如苯妥因（PHT）、苯巴比妥（PB）、卡马西平（CBZ）,其唾液浓度与血浓度密切相关[21．为抗癫痫药物的唾液浓度监测提供了广阔的应用和研究前景。近10年来一些新的抗癫痫药物陆续问世．新抗癫痫药物药动学如何？唾液浓度及与血液浓度相关性如何？作者查阅大量有关新抗癫痫药物血液与唾液浓度监测研究文献．综述如下：     

口服地戈辛片剂药物动力学比较

地戈辛(Digoxin)是广泛应用于临床治疗心衰的重要药物。由于临床用药剂量小,治疗量与中毒量又非常接近,易导致药物中毒。开展临床地戈辛血药浓度监测,指导临床安全、合理用药是十分必要的。临床使用的国产地戈辛片剂,往往来自不同制剂厂或同厂不同批号,药物在生物体中的吸收利用程度亦不尽相同,甚至出现很大的差异,而致使生物不等效。为全面、正确地评价药物制剂质量     

乙胺碘呋酮增加血清地戈辛浓度

由于治疗的复杂化,使药物之间相互作用的危险性增加。作者观察7例在接受地戈辛维持量治疗的患者,当加用乙胺碘呋酮(Amiodarone)时,突然出现毒性反应。为此作者研究应用乙胺碘呋酮时血清地戈辛浓度的反应。     

唾液浓度代替血清浓度进行茶碱治疗监测可行性的研究

氨茶碱是治疗支气管哮喘病的有效药物,但由于治疗范围狭窄(10～20μg/ml), 个体差异及毒副反应较大,临床应用受到一定限制。80年代以来,国内许多药学工作者进行了氨茶碱血药浓度监测和个体化给药的研究工作,为临床合理用药创造了有利条件.但测定血药浓度一般需多次自静脉取血,会给患者造成一定的损害和痛苦,不易为年老体弱和儿童患者接受。由于人们发现唾液中药物浓度通常与血清浓度相关,因此利用唾液作为样本,就成为一种简便的、无损害的、并能反应血药浓度的监测方法。     

苯妥英钠,卡马西平在血清,血清超滤液,唾液中浓度的监测和相关性探讨

本文应用超滤法测定血清中游离苯妥英钠、卡马西平浓度。并采用荧光偏振免疫法对患者血清、血清超滤液进行２种抗癫痫药物的测定及唾液中苯妥英钠液度的测定，研究它们的相关性。实验结果表明：唾液、超滤液中苯妥英钠浓度分别为血清药物浓度的１０．６３％和９．５１％，超滤液中卡马西平浓度为血清药物浓度的２２．５８％，且均具有良好的相关性，通过回收率及重现性试验证明本方法可用于常规监测。     

庆大霉素唾液药物浓度测定及临床意义

目的:探求唾液药物浓度与血药浓度的相关性及临床意义。方法:采用放射免疫法测定15例志愿受试者庆大霉素的唾液药物浓度和血药浓度。结果:血液、唾液中的庆大霉素浓度均在用药后1h达峰。结论:血液、唾液中的庆大霉素浓度呈正相关关系,即在庆大霉素治疗药物监测中唾液有可能代替血液。     

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.