皮肤微透析技术在药动学及药效学研究中的应用进展

目的:介绍皮肤微透析技术在药动学及药效学研究中的应用进展。方法:采用文献综述法,阐述国内、外近几年来将皮肤微透析技术应用于药动学及药效学研究的进展。结果与结论:皮肤微透析技术可以在不破坏皮肤组织的条件下对皮肤或皮下组织细胞外液物质浓度进行采样,与其他皮肤药动/药效学采样技术相比具有微创、实时、多位点等优点,可广泛应用于皮肤药动学和药效学研究。皮肤微透析技术在中药药动学及药效学研究中有很好的应用前景。     

微透析技术在皮肤药理学中的应用进展

微透析是一种活体的取样技术,在皮肤药理学的研究中应用广泛。微透析被用于外用制剂的生物等效性、制剂的透皮吸收、监测皮肤炎症介质、皮肤组织的内分泌、中药经皮代谢等相关研究。近年来,微透析向联用各种分析检测技术的方向发展,如联用超高效液相色谱、液质联用、酶标记免疫吸附测定等。然而,该技术本身也存在一些缺点,如油水分配系数较大药物的测定、低含量药物的测定、探针植入重现性等问题。文中综述了该技术的原理、优点、缺点及在皮肤药理学研究中的应用进展。     

微透析取样技术在中药体内分析中的应用研究进展

本文综述了微透析取样技术在中药体内分析中的应用,介绍微透析取样技术的原理、组成、探针类型、特点,重点阐述了微透析取样技术在测定脑、血液、皮肤等组织器官中中药有效成分浓度的应用实例。表明微透析取样技术在中药药效研究中具有广阔的前景。     

在体微透析技术应用于神经药动学研究进展

目的：综述目前在体微透析技术应用于神经药动学研究的实验室及临床结果。方法：检索近10年文献，综述评价。结果：微透析技术在作用于中枢神经系统药物动力学研究中具独特优势。结论：微透析技术在药物研究中具有极其重要、广泛的实用价值及应用前景。     

基于微透析技术的苦参碱凝胶经皮给药的药动学研究

目的 建立同步测定经皮给药制剂在皮肤、血液中药动学的方法,研究苦参碱凝胶在体内的药动学行为。方法 应用经体外和体内回收率校正建立的基于微透析探针的皮肤血液双位点同步微透析系统,通过在皮肤和颈静脉植入探针,在大鼠腹部脱毛部位给予苦参碱凝胶,连续收集探针中12 h的透析液,并采用LC-MS微量检测技术测定探针透析液中的药物浓度。结果 本研究成功构建了双位点同步微透析药动学评价系统,大鼠皮肤给予苦参碱凝胶后,皮肤中的药物浓度、AUC值、半衰期均显著高于血液中药物浓度。结论 本研究建立的微透析结合LC-MS的取样及检测技术为经皮给药制剂的药动学研究提供了新的技术平台。     

微透析联合LC-MS/MS法研究马钱子总碱囊泡凝胶透皮吸收

目的:建立皮肤微透析采样技术联合LC-MS/MS同时测定马钱子碱和士的宁的分析方法,并研究大鼠经皮给予马钱子囊泡凝胶后的透皮吸收。方法:应用皮肤微透析技术对大鼠给药部位皮下进行采样;微透析样品以他克林为内标,不经预处理直接进样;色谱采用XDB-C18柱,甲醇-乙腈-水(含0.05%甲酸和10 nmol·L-1甲酸铵)梯度洗脱;质谱采用正离子扫描多反应监测(MRM)方式。,用于定量的离子对分别为m/z 335.2→m/z 184.2(士的宁),m/z 395.2→m/z 324.2(马钱子碱),m/z 199.1→m/z 171.1(他克林)。结果:测定微透析样品中马钱子碱和士的宁2种成分的线性范围分别为0.195～50 ng.mL-1和0.156～40 ng.mL-1,日内和日间精密度(RSD)均小于15%,准确度、稳定性符合要求。结论:该方法操作简便、灵敏度高、专属性强,适用于皮肤微透析样品中马钱子碱和士的宁的测定。     

微透析（微灌注）技术在经皮给药制剂中的研究进展

通过梳理微透析（微灌注）技术的原理及特性,总结其在经皮给药制剂研究中的应用现状,分析了存在的问题和挑战,对未来发展方向进行展望,并提出相关建议,为该领域的进一步研究提供参考。     

微透析取样技术及其在药代动力学中的应用

本文综述了近年来国外有关微透析取样技术在药代动力学中的应用，介绍了微透析取样技术的原理、组成以及微透析探针的类型，重点介绍了在体微透析取样技术在动物和人药代动力学中的应用。表明微透析取样技术在药代动力学中的应用具有广阔的前景。     

微透析技术在药物-蛋白结合研究中的应用

目的 介绍微透析技术在药物-蛋白结合研究中的应用。方法 通过查阅近年来国内外相关文献,概述微透析技术的基本原理、特点、探针及影响探针相对回收率的主要因素,并重点介绍其在药物-蛋白结合研究中的应用。结果与结论 与平衡透析法、超滤法相比,微透析技术是一项新兴的在体或离体取样技术,在药物-蛋白结合研究中具有显著的优越性和广阔的应用前景。     

微透析技术在药物-蛋白结合研究中的应用

目的介绍微透析技术在药物-蛋白结合研究中的应用。方法通过查阅近年来国内外相关文献,概述微透析技术的基本原理、特点、探针及影响探针相对回收率的主要因素,并重点介绍其在药物-蛋白结合研究中的应用。结果与结论与平衡透析法、超滤法相比,微透析技术是一项新兴的在体或离体取样技术,在药物-蛋白结合研究中具有显著的优越性和广阔的应用前景。     

Applicability of reverse microdialysis in pharmacological and toxicological studies

A recent application of microdialysis is the introduction of a substance into the extracellular space via the microdialysis probe. The inclusion of a higher amount of a drug in the perfusate allows the drug to diffuse through the microdialysis membrane to the tissue. This technique, actually called as reverse microdialysis, not only allows the local administration of a substance but also permits the simultaneous sampling of the extracellular levels of endogenous compounds. Local effects of exogenous compounds have been studied in the central nervous system, hepatic tissue, dermis, heart and corpora luteae of experimental animals by means of reverse microdialysis. In central nervous studies, reverse microdialysis has been extensively used for the study of the effects on neurotransmission at different central nuclei of diverse pharmacological and toxicological agents, such as antidepressants, antipsychotics, antiparkinsonians, hallucinogens, drugs of abuse and experimental drugs. In the clinical setting, reverse microdialysis has been used for the study of local effects of drugs in the adipose tissue, skeletal muscle and dermis. The aim of this review is to describe the principles of the reverse microdialysis, to compare the technique with other available methods and finally to describe the applicability of reverse microdialysis in the study of drugs properties both in basic and clinical research.     

Intracerebral microdialysis: 30 years as a tool for the neuroscientist

1. Microdialysis is an established technique for studying physiological, pharmacological and pathological changes of a wide range of low molecular weight substances in the brain extracellular fluid. Many studies have proven its sensitivity in sampling the extracellular space in discrete brain locations, such as the striatum, and monitoring the action of exogenous substances. 2. The two main areas of application of microdialysis are the recovery of endogenous substances, primarily the neurotransmitters, and the infusion of drugs through the microdialysis cannula (retrodialysis). 3. Microdialysis in awake animals is the tool of choice for studying the relationship between changes in behaviour and neurotransmitters in certain brain areas. In addition, the concomitant recording of the electroencephalogram at the site of microdialysis has been shown to be extremely useful in determining the role of certain neurotransmitters in paroxysmal activity. 4. Clinical applications of microdialysis have included monitoring of ischaemic injury, subarachnoid haemorrhage, trauma and epilepsy. With the recent availability of standardized equipment, the use of microdialysis in the neurological clinic is likely to become more common.     

Application of microdialysis to characterize drug disposition in tumors

Microdialysis is an in vivo sampling technique that was initially developed to measure endogenous substances in the field of neurotransmitter research. In the past decade, microdialysis has been increasingly applied to study the pharmacokinetics and drug metabolism in the blood and various tissues of both animals and humans. This paper describes the general aspects of this in vivo sampling technique followed by the survey of the recent papers regarding the application of microdialysis to characterize anticancer drug disposition in solid tumors. It can be concluded that microdialysis is a very suitable method to obtain drug concentration-time profiles in the interstitial fluid of solid tumors as well as of other variety of tissues.     

Microdialysis as an Important Technique in Systems Pharmacology—a Historical and Methodological Review

Microdialysis has contributed with very important knowledge to the understanding of target-specific concentrations and their relationship to pharmacodynamic effects from a systems pharmacology perspective, aiding in the global understanding of drug effects. This review focuses on the historical development of microdialysis as a method to quantify the pharmacologically very important unbound tissue concentrations and of recent findings relating to modeling microdialysis data to extrapolate from rodents to humans, understanding distribution of drugs in different tissues and disease conditions. Quantitative microdialysis developed very rapidly during the early 1990s. Method development was in focus in the early years including development of quantitative microdialysis, to be able to estimate true extracellular concentrations. Microdialysis has significantly contributed to the understanding of active transport at the blood-brain barrier and in other organs. Examples are presented where microdialysis together with modeling has increased the knowledge on tissue distribution between species, in overweight patients and in tumors, and in metabolite contribution to drug effects. More integrated metabolomic studies are still sparse within the microdialysis field, although a great potential for tissue and disease-specific measurements is evident.     

Consequences of changes in BDNF levels on serotonin neurotransmission, 5-HT transporter expression and function: studies in adult mice hippocampus

In vivo intracerebral microdialysis is an important neurochemical technique that has been applied extensively in genetic and pharmacological studies aimed at investigating the relationship between neurotransmitters. Among the main interests of microdialysis application is the infusion of drugs through the microdialysis probe (reverse dialysis) in awake, freely moving animals. As an example of the relevance of intracerebral microdialysis, this review will focus on our recent neurochemical results showing the impact of Brain-Derived Neurotrophic Factor (BDNF) on serotonergic neurotransmission in basal and stimulated conditions. Indeed, although the elevation of 5-HT outflow induced by chronic administration of selective serotonin reuptake inhibitors (SSRIs) causes an increase in BDNF protein levels and expression (mRNA) in the hippocampus of rodents, the reciprocal interaction has not been demonstrated yet. Thus, the neurochemical sight of this question will be addressed here by examining the consequences of either a constitutive decrease or increase in brain BDNF protein levels on hippocampal extracellular levels of 5-HT in conscious mice.     

微透析技术在肿瘤药物研究中的应用进展

微透析技术具有连续动态微创取样优势,能实时在线研究正常生理和肿瘤病理情况下肿瘤药物在体内,尤其是肿瘤组织局部的分布、代谢和消除,利用PK/PD参数模型设计个体化给药方案,预防和减少肿瘤药物的毒性反应。同时,微透析技术还可以应用于肿瘤细胞外间质微环境中生化物质的监测以及肿瘤药物局部给药治疗,是肿瘤药物研究的重要技术手段。本文对近年来微透析在肿瘤药物研究中的应用进展进行检索和归纳,为微透析技术在取样、监测以及治疗领域的进一步研究应用提供参考。     

Microdialysis--theoretical background and recent implementation in applied life-sciences.

In the past decade microdialysis has become a method of choice in the study of unbound tissue concentrations of both endogenous and exogenous substances. Microdialysis has been shown to offer information about substances directly at the site of action while being well tolerable and safe. The large variety of its field of application has been demonstrated. However, a few challenges have to be met to make this method generally applicable in routine applications. This review will provide an overview over theoretical aspects that have to be considered during the implementation of microdialysis. Moreover, a comparison between microdialysis and other tissue sampling techniques will demonstrate advantages and limitations of the methods mentioned. Subsequently, it will present a critical synopsis of a variety of scientific/biomedical applications of this method with emphasis on the most recent literature, focussing on target tissues while giving examples of substances examined. It is concluded that microdialysis will be of great value in future investigations of pharmacokinetics, pharmacodynamics and in monitoring of disease status and progression.     

Ocular microdialysis: a continuous sampling technique to study pharmacokinetics and pharmacodynamics in the eye

The unique anatomy and physiology of the eye present many challenges to the successful development and delivery of ophthalmic drugs. Any therapeutic strategy developed to control the progression of anterior and posterior segment diseases requires continuous monitoring of effective drug concentrations in the relevant ocular tissues and fluids. Ocular microdialysis has gained popularity in recent years due to its ability to continuously monitor drug concentrations and substantially reduce the number of animals needed. The intrusive nature of ocular microdialysis experimentation has restricted these studies to animal models. This review article intends to highlight various aspects of ocular microdialysis and its relevance in examining the disposition of drugs in the anterior and posterior segments.     

Microdialysis in mice for drug delivery research

Intracerebral microdialysis was first performed in the mouse at the end of the 1980s. Most microdialysis studies on mice were confined to neuropharmacology and changes in neurotransmitter concentrations up to 1995, although pharmacological studies were done on other tissues like the skin, kidney and implanted tumors. The use of microdialysis in mice for pharmacokinetic and drug delivery studies owes much to the recent availability of genetically engineered mice, such as mice in which the genes encoding multiple drug resistance have been knocked out. The quantitative microdialysis of blood and various tissue fluids of the mouse is now feasible and the recent development of specific microdialysis devices for use in mice should facilitate its use in these small animals. This review covers the technical aspects of microdialysis in the mouse and includes references to many of the published studies on pharmacokinetics and drug delivery.     

Application of dermal microdialysis for the determination of bioavailability of clobetasol propionate applied to the skin of human subjects

Dermal microdialysis was used to assess the bioavailability of a topical corticosteroid, clobetasol propionate, following application onto the skin of human subjects. The penetration of clobetasol propionate from a 4% m/v ethanolic solution applied onto 4 sites on one forearm of healthy human volunteers was studied. A lipid emulsion, Intralipid?, was used as the perfusate and linear microdialysis probes with a 2-kDa cutoff were inserted intradermally at the designated sites. The results indicated that Intralipid could be used as a suitable perfusate for in vivo microdialysis of this lipophilic drug of interest. Furthermore, the study clearly demonstrated the application of dermal microdialysis as a valuable tool to assess the bioavailability/bioequivalence of clobetasol propionate penetration into the skin following topical application.