以经皮微渗析技术涂抹表皮生长因子的小猪在体经皮吸收研究

目的研究表皮生长因子的经皮渗透性，并考察透皮吸收促进剂月桂氮酮（Azone）对其经皮渗透性的影响。方法以广西小型猪为实验模型动物，应用经皮微渗析在体取样技术进行实验。探针的在体回收率以反向渗析法测定。结果Azone可以极人地提高药物在渗析液及皮肤中的浓度，2％和5％的Azone分别使渗析液中药物的稳态流量从0.001μg/h提高到1．281和1．824μg／h。结论经皮微渗析技术是研究药物在体经皮吸收的有力工具。Azone是表皮生长因子经皮吸收的优良促进剂。     

以经皮微渗析技术研究奥旦西酮的大鼠在体经皮吸收

目的：研究奥旦西酮的经皮渗透性,并考察透皮吸收促进剂月桂氮　酮(azone)对其经皮渗透性的影响。方法：以大鼠为实验模型动物,应用经皮微渗析在体取样技术进行实验。探针的在体回收率以反向渗析法测定。结果：Azone可以极大地提高药物在渗析液及皮肤中的浓度,2%和5%的azone分别使渗析液中药物的稳态流量从0.001 μg.h^-1提高到1.281和1.824 μg.h^-1。结论：经皮微渗析技术是研究药物在体经皮吸收的有力工具。Azone是奥旦西酮经皮吸收的优良促进剂。     

微透析技术及其在经皮给药系统中的应用

综述了经皮微透析技术及其近年来在经皮给药系统中的应用,包括经皮吸收药物的药动学研究及生物利用度和生物等效性评价。     

利多卡因凝胶经皮吸收的动力学和药效学

目的研究利多卡因凝胶的经皮吸收动力学以及药效学。方法用经皮微渗析的方法测定大鼠真皮内药物浓度的变化,计算相关参数;用电刺激法考察药效,并与市售EMLA(eutectic mixture of local anesthetics)霜剂进行药效比较。结果持续用药1 h,利多卡因经皮吸收动力学曲线在1.25 h达到峰值;起效时间与EMLA霜剂相近,局麻作用维持时间和局麻强度优于EMLA。结论利多卡因凝胶具有良好的局麻作用;局部用药后,利多卡因产生局部麻醉作用的真皮中最低有效浓度为12 mg·L^-1。     

微渗析技术研究克拉霉素亚微乳剂相分布

目的:利用微渗析技术研究克拉霉素(clarithromycin,CLA)亚微乳剂相分布,考察离子对增溶剂及NaOH用量对乳剂相分布的影响.方法:以维生素E琥珀酸酯(tocopherol succinate,TS)、油酸为离子对增溶剂,制备CLA亚微乳剂;浓差法测定探针回收率与传递率,以亚微乳剂为渗析介质,用反相渗析法测定回收率.结果:反相渗析法测得回收率为86.2%;90%以上的药物分布于乳剂油相中.结论:微渗析技术可以用于测定乳剂的相分布,TS促进CLA于乳剂油相分布的能力更强,且对体系pH值变化较不敏感.     

微渗析技术在药代动力学和药物代谢研究中的应用

1　前言微渗析 (ｍｉｃｒｏｄｉａｌｙｓｉｓ)是一种在体取样技术 (ｉｎｖｉｖｏｓａｍｐｌｉｎｇｔｅｃｈｎｉｑｕｅ) ,是在线渗析技术的一个分支。最早由美国和瑞典的研究人员首先提出了这一概念[1] 。他们的构思是在动物组织内植入一个“人工毛细血管” ,用生理溶液 (灌注液 ,ｐｅｒｆｕｓａｔｅ)对其进行灌注 ,组织细胞间液中的分子则可以通过管壁进入渗析液 (ｄｉａｌｙｓａｔｅ) ,然后通过对渗析液中的物质进行分析来反映组织液中物质组成。这一技术自 80年代初逐步发展成熟起来 ,首先成为实验精神药理学和神经生理学的一个有力的实验…     

微渗析技术用于盐酸奥旦西酮的大鼠在体透皮吸收研究

本文进行了微渗析探针的体内、外校正,浓差法和反渗析法分别用于测定探针的体内和体外回收率。在探针校正的基础上,研究了盐酸奥旦西酮（ＯＮ）丙二醇（ＰＧ）溶液的大鼠在体经皮吸收及渗透促进剂油酸（ＯＡ）的作用。微渗析样品用高效液相法测定。结果证明：探针的体外回收率（３５．４６±４２％）和体内回收率（３２．５３±１．８％）没有显著的差别（Ｐ＞０．１）。以 ２％和５％ＯＡ的ＰＧ溶液为渗透促进剂时,ＯＮ在渗析液和真皮中达到坪浓度的时间分别为３．５及１．５ ｈ：后者的坪浓度约是前者的两倍。当ＯＡ的浓度从０提高到２％、 ５％时,药物的稳态传递速度从０．００１增大到０．０３０和０．０５８μｇ·ｈ~－１。实验证明 ＯＡ对于ＯＮ的大鼠在体透皮吸收是一种有效的促进剂。     

组织工程化皮肤在药物经皮吸收研究中的应用

目的：介绍组织工程化皮肤在药物经皮吸收研究中的应用。方法：查阅文献，简要综述组织工程化皮肤的特征及其在药物经皮吸收研究中的应用情况，结果：组织工程化皮肤已用于药物经皮吸收的研究。结论：组织工程化皮肤作为药物经皮吸收研究的模型值得进一步推广。     

用在体皮肤微透析法研究黄芩苷凝胶经大鼠皮肤吸收的局部药动学

目的建立大鼠在体皮肤微透析技术,研究黄芩苷凝胶经皮吸收局部药动学。方法采用HPLC-MS/MS联用技术测定大鼠皮肤微透析液中黄芩苷的浓度。SD大鼠在麻醉状态下做皮肤微透析预处理,然后将黄芩苷凝胶涂于探针所在皮肤表面,收集皮肤微透析液样品进行黄芩苷浓度测定,绘制黄芩苷浓度-时间曲线,计算经皮吸收局部药动学参数。结果用于定量分析的离子对为m/z 447.3→271.2,黄芩苷在检测浓度范围内线性关系良好,色谱的专属性、精密度等测定结果均符合生物样品测定要求。体内皮下探针对黄芩苷的回收率为（24.40±0.91）%,240 min内各取样点回收率保持稳定;黄芩苷经皮给药后8 h内微透析液中均可检测到黄芩苷的存在,且药物在皮肤组织内浓度持续升高,AUC0-t为（50.04±34.17）（mg·min）/L。结论在体皮肤微透析法可用于黄芩苷经皮吸收局部药动学研究。     

微乳给药系统研究概况

微乳是一种热力学及动力学稳定的、乳滴小于0．1μm的特殊乳剂,可作为脂溶性和水溶性药物载体,促进药物的口服或经皮吸收并具有靶向性。本文综述了微乳的制备工艺及在药物制剂中的应用。     

微透析-高效液相色谱法联用研究吴茱萸提取物的经皮吸收药动学特性

目的:利用在体皮肤微透析技术研究吴茱萸提取物经皮吸收的特性。方法:以裸鼠为研究对象,建立在体经皮微透析采样技术,以吴茱萸碱和吴茱萸次碱为指标成分,采用高效液相色谱测定吴茱萸提取物经皮给药后透析液中的药物浓度,通过相对损失率的校正,计算皮肤药物浓度,并利用Kinetica 5.0软件对皮肤药物浓度和时间进行非房室模型拟合,计算相关统计参数。结果:吴茱萸提取物中吴茱萸碱的达峰时间为(150±15.3)min,半衰期(t_1/2)(263.7±41.6)min;吴茱萸次碱的达峰时间为(90±2.1)min,半衰期(t_1/2)(194±17.3)min;二者均能较快地达到峰值,并在较长的时间内保持稳定释放,使皮下组织中的药物浓度保持在一个相对恒定的水平。结论:本研究中所建立的微透析方法可用于吴茱萸提取物的皮肤药动学研究,吴茱萸碱和吴茱萸次碱可透过皮肤吸收而发挥临床药效。     

Percutaneous absorption and metabolism of 2-butoxyethanol in human volunteers: a microdialysis study

We determined percutaneous absorption kinetics of 2-butoxyethanol (BE) in volunteers using microdialysis. Four male volunteers were dermally exposed twice to 90% and 50% aqueous solutions (v/v) of BE for 4.5h. To determine percutaneous absorption kinetics the concentration of BE was measured in the dialysate samples collected at 30 min-intervals throughout exposure. The systemic absorption, which is needed to determine recovery of the BE in the dialysate, was estimated from the concentration of the main metabolite of BE, free butoxyacetic acid (BAA) in urine. A pseudo steady-state percutaneous absorption was reached approximately at 2h of exposure for both BE concentrations. The maximum dermal flux of 50% BE was higher than that of 90% BE (2.8+/-0.4, 1.9+/-0.6 mg cm(-2)h(-1), respectively). The more diluted BE solution showed shorter lag time: 25 min versus 39 min. The amount of BAA was determined in the pooled dialysate samples collected at 4 and 4.5h. The dermal metabolism seems to be low, the BAA amount ranged from 0.03% to 1.9% of the BE in the same dialysate. Our study demonstrates applicability of microdialysis technique for assessment of percutaneous absorption kinetics and dermal metabolism without interference from the systemic compartment.     

Discrepancies between different rat models for the assessment of percutaneous penetration of hazardous substances

By regulatory authorities the rat is considered to be a suitable animal model to predict the percutaneous absorption of hazardous substances in humans. In our study, the percutaneous penetration of 2-butoxyethanol (BE) and toluene was compared in different rat models. Intradermal microdialysis and static diffusion cells were used in in vivo and in vitro experiments with haired Wistar and hairless Lewis rats. Microdialysis experiments showed a steady-state penetration for BE and a penetration maximum for toluene in both rat strains at ∼60 min after beginning of exposure. However, in diffusion cell experiments the penetration of the test compounds in both rat strains increased until the end of exposure (4 h). Additionally, in microdialysis experiments BE penetrated in hairless rats in a higher amount than in haired rats (factor: 1.4; P < 0.01), for toluene it was just the opposite (factor: 1.9; P < 0.001). In diffusion cell experiments, the penetrated amounts of both compounds were higher in hairless rats compared to haired rats. The fluxes for BE were in diffusion cell experiments at a factor of 14.5 (haired rat) and 18.1 (hairless rat) higher than in microdialysis experiments, the difference factor for toluene was 2.6 (haired rat) and 12.9 (hairless rat). The lag times indicate a significantly faster penetration in microdialysis experiments compared with diffusion cell experiments (P < 0.001). There are great differences in percutaneous penetration behaviour between the techniques and the rat strains. The diffusion cell method has difficulties to describe the percutaneous penetration kinetics, whereas microdialysis describes it more reliable. Due to these differences the reliability of a conversion factor for the transfer of percutaneous absorption data from rat to human skin, as proposed in the literature, is questionable.     

In vivo study of percutaneous absorption of 4-chloroaniline using microdialysis in the rat

The present work was undertaken to study the percutaneous absorption of 4-chloroaniline (parachloroaniline, PCPA, CAS 106-47-8), a chemical intermediate in pesticide manufacture, using in vivo microdialysis in the rat. The results of the microdialysis study showed that PCPA was able to cross the skin (Tmax = 3 h and area under the curve (AUC) = 332.1 ng.h/ml) and rapidly enter the systemic circulation (Tmax = 3.3 +/- 0.6 h). It could be also shown that PCPA was partly metabolised during its percutaneous absorption. The analysis of cutaneous dialysate samples using gas chromatography/mass spectrometry (GC-MS) showed that the metabolite was 4-chloracetanilide. Taken together, the data obtained showed that contact with the skin is a danger for exposed persons.     

Microdialysis for the evaluation of penetration through the human skin barrier — a promising tool for future research?

The direct measurement of local drug concentration levels at discreet skin locations with minor trauma has recently become possible with the introduction of cutaneous microdialysis. Cutaneous microdialysis is an in vivo sampling technique for measuring solutes in the extracellular fluid of the dermis. When used in combination with other experimental approaches, for example with a variety of non-invasive techniques to describe the functional status of the skin (bioengineering methods), it may help investigators to gain new insights into the fields of skin diseases, metabolism and drug absorption/penetration. An important parameter to describe the efficacy of microdialysis is the relative recovery. This is the ratio between the concentration of a substance in the dialysate and the true extracellular concentration. Several methods are in common use to describe the relative recovery (no-net-flux method or retrodialysis). Parameters such as probe design, depth of the probe in the dermis, physico-chemical properties of the compound of interest, and analytical aspects are important factors influencing microdialysis. Microdialysis has been used to investigate the influence of penetration enhancers, vehicles or iontophoresis on percutaneous absorption, performed by in vivo studies in rats. In human volunteers, most of the experiments have been performed to study the kinetics of fast penetrating substances, e.g. nicotine, non-steroidal antiinflammatory drugs, local anaesthetics, or solvents. Problems have been encountered in the detection of lipophilic and highly protein-bound substances. Further, dermal metabolism and the influence of barrier perturbation on percutaneous absorption have been analyzed. Investigations suggest that microdialysis, in combination with traditional techniques, might give valuable information regarding the assessment of the penetration of drugs and other exogenous agents through the skin. In spite of the clearly defined and accepted advantages of microdialysis technology for studies of transdermal drug delivery, to date no standardized test procedure exists nor has the reproducibility of the results been evaluated. In the future, these problems have to be solved to enable this method to find its place in standard research.     

Methods for measuring in-vivo percutaneous absorption in humans

In-vivo human data on percutaneous absorption are scarce, although they are indispensable for health risk assessment of dermal exposure. In addition, they are considered to be the gold standard for the evaluation of in-vitro systems as well as predictive mathematical models. Dermal absorption in vivo can be assessed using different approaches. The most used methods for determination of in-vivo dermal absorption are the measurement of the parent chemical and/or its metabolite level in biological material, the microdialysis technique and stratum corneum tape stripping. Recently, the non-invasive spectrophotometric methods based on infrared and Raman spectroscopy showed themselves as promising tools for studying percutaneous absorption though these approaches are still in their developmental stages and requires further optimization and validation. The aim of this article is to review different methods for determination of percutaneous absorption in vivo in humans. The advantages and limitations are discussed with respect to generating data for comparison with in-vitro or predictive mathematical models or health risk assessment of chemicals. Furthermore, the importance of the volunteer experiments in generating relevant data for human risk assessment as well as for the development and implementation of biological monitoring in occupational settings will be addressed.     

Percutaneous penetration kinetics of lidocaine and prilocaine in two local anesthetic formulations assessed by in vivo microdialysis in pigs

The aim of this study was to characterize and compare the percutaneous penetration kinetics of lidocaine (L) and prilocaine (P) in two local anesthetic formulations by in vivo microdialysis coupled with HPLC. The microdialysis system for studying lidocaine and prilocaine was calibrated by a no-net-flux method in vitro and retrodialysis method in vivo, respectively. A dosage of 0.2 g/cm2 of an in-house P-L formulation (2.5% lidocaine and 2.5% prilocaine, methylcellulose-based) and commercially available Eutectic Mixture of Local Anesthesia (EMLA, 2.5% lidocaine and 2.5% prilocaine, carbopol-based) was separately but symmetrically applied in the dorsal region of pigs. Saline (0.9%, w/v) was perfused into the linear microdialysis probe at a flow rate of 1.5 microl/min. Dialysate was collected upon topical application up to 6 h at 20-min intervals and assessed by HPLC. The results demonstrated the area under the concentration-time curve (AUC(0-6 h)) of lidocaine and prilocaine in EMLA was 71.95+/-23.36 microg h/ml and 38.01+/-14.8 microg h/ml, respectively, in comparison to 167.11+/-56.12 microg h/ml and 87.02+/-30.38 microg h/ml in the P-L formulation. The maximal concentrations (Cmax) of lidocaine and prilocaine in the dermis were 29.2+/-9.08 microg/ml and 16.54+/-5.31 microg/ml in EMLA and 80.93+/-17.98 microg/ml and 43.69+/-12.87 microg/ml in the P-L formulation, respectively. This study indicates a well-calibrated microdialysis system can provide vital real-time information on percutaneous drug delivery and specifically a methylcellulose-based P-L formulation can increase percutaneous absorption of both lidocaine and prilocaine in pigs compared to carbopol-based EMLA.     

Comparison of Franz cells and microdialysis for assessing salicylic acid penetration through human skin

The purpose of the present study was to compare Franz cells (FC) and microdialysis (MD) for monitoring the skin absorption of salicylic acid (SA). The influence of pH on SA flux was also assessed by these two techniques.Excised abdominal human skin was used in the experiments. SA was dissolved in phosphate buffer solutions of pH 2, 5 and 7 (2 mg/ml). SA concentrations in the receptor FC solutions and in MD samples were assessed by high performance liquid chromatography (HPLC). The results demonstrate that the flux of SA decreased with increased pH. The profiles permeation determined by Franz cells and microdialysis were similar. However, whatever the pH, the SA flux was higher with microdialysis than with Franz cells.The results showed that SA percutaneous permeation conformed to the pH partition hypothesis. The flux of SA was different when it was determined by the two techniques. The collect of SA, by these two techniques is different. The results of the two techniques are compared and discussed.