Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Microdialysis”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 91 records · Page 5Linked to original sources

Brain microdialysis in exercise research.

During the last 5 to 10 years, the microdialysis technique has been used to explore neurotransmitter release during exercise. Microdialysis can collect virtually any substance from the brains of freely moving animals with a limited amount of tissue trauma. It allows the measurement of local neurotransmitter release in combination with ongoing behavioural changes such as exercise. Several groups examined the effect of treadmill running on extracellular neurotransmitter levels. Microdialysis probes were implanted in different brain areas to monitor diverse aspects of locomotion (striatum, hippocampus, nucleus accumbens, frontal cortex, spinal cord), food reward (hypothalamus, hippocampus, cerebral cortex), thermoregulation (hypothalamus). Some studies combined microdialysis with running on a treadmill to evaluate motor deficit and improvement following dopaminergic grafts in 6-hydroxydopamine lesioned rats, or combined proton nuclear magnetic resonance spectroscopy and cortical microdialysis to observe intra- plus extracellular brain glucose variations. This method allows us to understand neurotransmitter systems underlying normal physiological function and behaviour. Because of the growing interest in exercise and brain functioning, it should be possible to investigate increasingly subtle behavioural and physiological changes within the central nervous system. There is now compelling evidence that regular physical activity is associated with significant physiological, psychological and social benefits in the general population. In contrast with our knowledge about the peripheral adaptations to exercise, studies relating exercise to brain neurotransmitter levels are scarce. It is of interest to examine the effect of short and long term exercise on neurotransmitter release, since movement initiation and control of locomotion have been shown to be related to striatal neurotransmitter function, and one of the possible therapeutic modalities in movement, and mental disorders is exercise therapy. Until very recently most experimental studies on brain chemistry were conducted with postmortem tissue. However, in part because of shortcomings with postmortem methods, and in part because of the desire to be able to directly relate neurochemistry to behaviour, there has been considerable interest in the development of 'in vivo' neurochemical methods. Because total tissue levels may easily mask small but important neurochemical changes related to activity, it is important to sample directly in the extracellular compartment of nervous tissue in living animals. Since the chemical interplay between cells occurs in the extracellular fluid, there was a need to access this compartment in the intact brain of living and freely moving animals. Estimation of the transmitter content in this compartment is believed to be directly related to the concentration at the site where these compounds are functionally released: in the synaptic cleft. As measurements in the synapse are not yet possible, in vivo measurements in the extracellular fluid appear to provide the most directly relevant information currently available. This article provides an overview of the in vivo microdialysis technique as a method for measuring in the extracellular space, and its application in exercise science. Although this technique has been used in different tissues such as brain, adipose tissue, spinal cord and muscle, in animals as well as humans, we will focus on the use of this in vivo method in brain tissue. Recently two excellent reviews on the application of microdialysis in human experiments especially in subcutaneous tissue have been published, and we refer the interested reader to these articles.

Animals↗

Microdialysis in drug discovery.

Microdialysis has been developed during the last 25 years by several authors primarily to study brain function and changes in levels of endogenous compounds such as neurotransmitters or metabolites. The development of microdialysis for the purpose of measuring drugs was initiated during the late eighties. This technique provides a means of continuous plasma sampling without repeated blood sampling and the applicability to the study of drug metabolism and pharmacokinetics in experimental animals and human. Also, the microdialysis technique allows the study of plasma protein binding and the saturation of protein binding. The implantation of the microdialysis probe in other tissues and organs, like central nervous system, adipose tissue and heart, allows the study of drug distribution. On the other hand, the measurement of endogenous substances using the microdialysis technique permits the study of the effect of drugs on neurotransmission and metabolism. Moreover, as this technique allows the simultaneous determination of different physiological parameters such as blood pressure, locomotor and convulsive activity, it is a suitable tool for pharmacokinetic-pharmacodynamic studies of drugs and pharmacokinetic-pharmacodynamic (PK-PD) modeling. Lastly, the reverse microdialysis is a powerful technique for the study of local actions of drugs in different tissues such as specific brain nuclei, myocardium, liver or skeletal muscle. So, this article reviewed the vast applications of the microdialysis technique for the study of pharmacokinetic and pharmacodynamic properties of drugs.

Animals↗

Microdialysis of the brain structures: application in behavioral research on vasopressin and oxytocin.

In vivo microdialysis allows sampling of brain regions in conscious, freely moving animals. Moreover, the in vivo microdialysis allows to administer drugs directly into specific brain areas. Both are useful in behavioral studies. The subject of this review is the methodology of brain microdialysis, that is construction of the probe, effect of temperature, composition of the perfusion medium, perfusion flow rate, characteristics of the membrane material and the role of the diffusion coefficient. Other techniques of the study of in vivo release, alternative for microdialysis, are described. Advantages and disadvantages of acute and chronic microdialysis are discussed. Chronic microdialysis is especially needed in behavioral studies. Finally, the examples of application of microdialysis in behavioral studies of vasopressin (AVP) and oxytocin (OXT) and our own experience in these studies are described.

Animals↗

Bedside-microdialysis for early detection of vasospasm after subarachnoid hemorrhage. Case report and review of the literature.

Continuous monitoring of cerebral metabolism would be desirable for early detection of vasospasm in SAH patients. Bedside-microdialysis, a new technique for on-line monitoring of cerebral metabolism, may reflect changes seen in cerebral vasospasm diagnosed by transcranial Doppler sonography (TCD). This report represents the first case of combined TCD monitoring and on-line microdialysis from the brain extracellular fluid in a SAH patient. A 48-year-old woman suffered subarachnoid hemorrhage grade IV according to Hunt and Hess. Angiography revealed an aneurysm of the left carotid artery. The aneurysm was clipped 45 hours after bleeding. The microdialysis catheter was inserted after aneurysm clipping into the white matter of the left temporal lobe. Sampling of microdialysates started immediately, analyzing time for glucose, lactate, pyruvate and glutamate was four minutes. Postoperatively, the patient was doing well and microdialysis and TCD parameters remained within normal range. On the third postoperative day a shift to anaerob metabolism (decrease of glucose, increase of lactate and the lactate-pyruvate ratio up to pathological levels) and an increase in glutamate was observed suggesting insufficient cerebral perfusion. The patient progressively deteriorated clinically. Vasospasm was diagnosed by TCD monitoring 36 hours after onset of ischemic changes monitored by microdialysis. After elevation of mean arterial blood pressure, TCD values and metabolic parameters normalized. Interestingly, the pathological changes in on-line microdialysis preceded the typical increase in blood flow velocity by TCD and the clinical deterioration. Our case suggests, that bedside-microdialysis may be useful for early detection of vasospasm and continuous surveillance of treatment and may be a new guide to treat ischemic neurological deficits following SAH.

Brain↗

Human pharmacokinetics of L-3,4-dihydroxyphenylalanine studied with microdialysis.

BACKGROUND: Intravenous and subcutaneous microdialysis was performed to compare the free concentrations and pharmacokinetics of L-3, 4-dihyroxyphenylalanine (L-dopa) in blood and tissue in healthy subjects and in patients with Parkinson disease. METHODS: Nine healthy volunteers and 10 patients with Parkinson disease, stage 1. 5-2 according to the Hoehn-Yahr rating scale, took part of the study. In the patient group subcutaneous microdialysis and ordinary blood sampling were performed, whereas in the control group intravenous microdialysis was also performed. Microdialysis samples were collected in fractions of 15 min. The first two fractions were collected for analysis of basal concentrations. A blood sample was also taken. The patients were then given one tablet of Madopar((R)) (100 mg of L-dopa and 25 mg of benserazide), and the microdialysis was continued for another 210 min. Blood samples were obtained at 30-min intervals. RESULTS: The serum samples gave a significantly higher mean area under the curve (AUC; 491 +/- 139 micromol. min/L) than that for intravenous dialysates (235 +/- 55.3 micromol. min/L), suggesting a protein binding of 50%. The L-dopa concentrations from the subcutaneous dialysates matched those from the intravenous dialysates, indicating rapid distribution of L-dopa to the tissues. CONCLUSIONS: Parkinsonian patients in early stages of the disease have a pharmacokinetic pattern of free L-dopa similar to that of healthy subjects. Comparison of AUCs from microdialysis with ordinary serum analysis revealed data indicating significant protein binding. Microdialysis is a suitable and easily applied tool in pharmacokinetic studies.

Adult↗

In vivo microdialysis for the investigation of drug levels in the dermis and the effect of barrier perturbation on cutaneous drug penetration. Studies in hairless rats and human subjects.

The thesis opens with review chapters concerning theoretical and practical aspects of the investigation of drug contents in the skin. A discussion of the advantages and limitations of the established methods as well as the relatively new sampling method of microdialysis, which is employed in the experimental section, is given. Factors influencing the barrier function of the normal human skin are described as are the alterations in skin barrier function found in diseased and experimentally barrier perturbed skin. The microdialysis technique consists of introducing an ultra thin, semipermeable tube, a so-called probe, in the dermis. The tube is connected to a precision pump, which provides a steady flow of a tissue-compatible fluid through the probe at a very low flow. Smaller molecules in the tissue, among them the non-protein bound fraction of the drug content in the extracellular fluid, will passively diffuse across the surface of the membrane and thus enter the flow of the perfusate, which is sampled at regular intervals and analysed. Microdialysis is used for the determination of drug levels in the skin after topical as well as systemic drug delivery in the experimental part of the thesis. The method is not applicable to the investigation of all drugs or compounds, as we have shown that it is not feasible to sample highly protein-bound drugs or very lipophilic drugs by microdialysis without further development of the method. The investigation of topical drug administration consists of 2 studies of cutaneous penetration of a model drug, salicylic acid, initially investigated in hairless rats and subsequently in human volunteers. In both studies, barrier perturbation of the skin was undertaken by physical (removal of the stratum corneum by repeated tape stripping) or chemical (treatment with acetone) methods or by provocation of irritative dermatitis (by application of sodium lauryl sulphate, a detergent). Prior to the penetration experiment, the barrier damage inflicted was quantified by non-invasive measurements of transepidermal, water loss and erythema. The penetration of salicylic acid, applied in an ethanol solution in chambers glued to the skin in the barrier perturbed areas, was measured by microdialysis sampling of the drug level in the underlying dermis. At the end of the experiment, probe depth in the dermis and skin thickness were measured by ultrasound scanning. In humans and hairless rats alike, the cutaneous drug penetration was highly increased in tape stripped skin (157- and 170-fold increased, respectively, in comparison to the penetration in unmodified skin) and in skin with irritative dermatitis (46- and 80-fold increased). Delipidization by acetone led to a doubling of the penetration in humans but had no effect on penetration in hairless rats. In both studies a close correlation between the measurements of barrier perturbation by non-invasive methods and the cutaneous drug penetration in the same area was found. In the human study, the barrier perturbation in the acetone treated area was not measurable by non-invasive methods, whereas drug penetration, measured by microdialysis sampling, was significantly increased, indicating that the microdialysis method possesses high sensitivity in the detection and quantification of perturbed skin barrier function. In the human study, a dose-response relationship between the concentration of detergent used for the induction of irritant dermatitis and the ensuing increase in drug penetration across the skin could be demonstrated. In the hairless rat study a correlation between probe depth in the dermis and drug penetration was found, demonstrating that the more superficially a probe was placed, the earlier it would be reached by the influx of drug across the skin. Systemic drug distribution was studied in healthy volunteers following oral administration of 2 g acetylsalicylic acid. (ABSTRACT TRUNCATED)

Administration, Cutaneous↗

Cutaneous microdialysis. Methodology and validation.

This thesis describes the methodology and validation of cutaneous microdialysis for the study of skin penetration of various topically applied substances in experimental dermatological research. Microdialysis is a sampling technique which makes it possible to measure substances in the extracellular water space in human and animal skin in vivo. A microdialysis probe, i.e. a tubular semipermeable membrane connected to afferent and efferent tubings, is placed in the dermis and perfused. Substances from extracellular space may diffuse through the pores of the membrane and be collected in the dialysate for further analysis. Glucose, sodium fusidate, betamethasone 17,21-dipropionate and calcipotriol were chosen as model substances and were investigated by in vitro microdialysis. The perfusion rate, the length of the membrane, stirring rate and temperature influenced recovery of the substances. Lipophilic compounds tend to have low recoveries and differ in recovery and loss. Insertion of the microdialysis probe causes a trauma in the skin. Rat and human skin were studied in vivo. Increase in skin blood flow, erythema and skin thickness were demonstrated by laser Doppler perfusion imaging, Dermaspectrometer colorimetry, Minolta Chromameter colorimetry and ultrasound imaging of cross-sectional skin structure. In addition histamine was released in rat skin due to the needle insertion. An equilibration period of minimum 90 min in human skin and 30 min in rat skin after the insertion is necessary to allow the effects of trauma to diminish. To obtain measurable concentrations in the dialysate in rats treated topically with the lipophilic drug betamethasone 17-valerate, unrealistic high doses and penetration enhancement were required. The highly protein-bound drug fusidic acid was not measurable in the dialysate after topical application, probably due to very low concentrations of free diffusible drug. Measurable concentrations were only observed after high doses of oral administrations of fusidic acid. Calcipotriol could not be detected in the dialysate. The microdialysis technique is probably primarily useful for the study of hydrophilic substances and substances with low protein binding and low molecular weight. However, application of cutaneous microdialysis for the study of lipophilic substances need further methodologically development.

Animals↗

Microdialysis for pharmacokinetic analysis of drug transport to the brain.

The intracerebral microdialysis technique represents an important tool for monitoring free drug concentrations in brain extracellular fluid (brain(EcF)) as a function of time. With knowledge of associated free plasma concentrations, it provides information on blood-brain barrier (BBB) drug transport. However, as the implantation of the microdialysis probe evokes tissue reactions, it should be established if the BBB characteristics are maintained under particular microdialysis experimental conditions. Several studies have been performed to evaluate the use of intracerebral microdialysis as a technique to measure drug transport across the BBB and to measure regional pharmacokinetics of drugs in the brain. Under carefully controlled conditions, the intracerebral microdialysis data did reflect passive BBB transport under normal conditions, as well as changes induced by hyperosmolar opening or by the presence of a tumor in the brain. Studies on active BBB transport by the mdr1a-encoded P-glycoprotein (Pgp) were performed, comparing mdr1a(-/-) with wild-type mice. Microdialysis surgery and experimental procedures did not affect Pgp functionality, but the latter did influence in vivo concentration recovery, which was in line with theoretical predictions. It is concluded that intracerebral microdialysis provides meaningful data on drug transport to the brain, only if appropriate methods are applied to determine in vivo concentration recovery.

Journal Article↗

Validation of subcutaneous microdialysis sampling for pharmacokinetic studies of flurbiprofen in the rat.

The objective of this study was to validate subcutaneous (sc) microdialysis sampling to study flurbiprofen pharmacokinetics and plasma protein binding in the awake freely moving rat. A linear microdialysis probe was manufactured using a Hemophane hollow fiber which was tested in vitro and in vivo for the recovery of flurbiprofen and naproxen used as retrodialysis marker. Flurbiprofen was administered intraperitoneally and intravenously at a dose of 20 mg/kg in rats. In both cases, conventional blood sampling and sc microdialysis sampling were simultaneously performed. The microdialysates were analyzed on-line by high-pressure liquid chromatography. Naproxen, which was shown to have a similar in vivo loss by retrodialysis as flurbiprofen (71.5 +/- 0.9% and 71.0 +/- 0.8% respectively, n = 3), was used to continuously monitor probe recovery. Concentration-dependent protein binding of flurbiprofen was demonstrated in vivo based on experiments with a simultaneous sc microdialysis and blood sampling. Values of unbound fraction were similar to those reported previously by intravenous microdialysis sampling, demonstrating that the sc unbound concentrations are very similar to those in the central compartment. There was no significant difference among pharmacokinetic parameters (AUC, CL, t(1/2z), Vd) for total or unbound flurbiprofen determined after intraperitoneal and intravenous administration. Subcutaneous microdialysis is a simple yet powerful tool to study the pharmacokinetics and the in vivo plasma protein binding of flurbiprofen in the awake unrestrained rat.

Animals↗

Fluconazole distribution in rat dermis following intravenous and topical application: a microdialysis study.

The objective of this study was to investigate the skin distribution of fluconazole, a water-soluble antifungal agent, following intravenous (i.v.) and topical administration in the awake freely moving rat. Following i.v. bolus injection of fluconazole (10 mg/kg), a dual-site microdialysis sampling was performed in jugular vein and dermis in five rats. In addition, cutaneous absorption was studied by dermal microdialysis sampling following topical application of Diflucan Gel 0.5% to 12 rats. Fluconazole microdialysate concentrations were measured by on-line HPLC. To calibrate in vivo the probes, a fluorinated analog (UK-54737) of fluconazole was used as retrodialysis marker after demonstrating that recoveries were no different. Following i.v. bolus injection, fluconazole rapidly penetrates into the dermis. Cutaneous microdialysis sampling provided dermal concentrations of fluconazole, which were very similar to the unbound plasma concentrations determined by vascular microdialysis. The distribution equilibrium was rapidly achieved with a dermis-to-plasma partition coefficient of 1.02+/-0.04 (n=5). Following topical application of 0.5 g of Diflucan Gel containing 0.5% of fluconazole, active unbound concentrations in dermis were measured by cutaneous microdialysis for 11 h after application. The area under the curve (AUC) of fluconazole in dermal dialysate was relatively constant to an implantation depth of approximately 350 microm. Below this depth, the AUC progressively decreased with increasing implantation depth of the probe. Finally, this study shows that cutaneous microdialysis is an effective and minimally invasive tool to evaluate the dermal pharmacokinetics of fluconazole following intravenous or topical administration.

Administration, Topical↗

An in vitro hydroxyl radical generation assay for microdialysis sampling calibration.

A xanthine oxidase hydroxyl radical (.OH)-generating system was created for sustained in vitro production of *OH. This assay was coupled with microdialysis sampling to elucidate the factors that influence microdialysis calibration during radical trapping. A *OH trapping agent, 4-hydroxybenzoic acid, was included either in the microdialysis perfusion fluid or in the medium external to the microdialysis probe. Xanthine oxidase enzymatic activity was reproducible and had an average activity measured by UV absorbance of produced uric acid of 0.037 +/- 0.005 deltaAU/min (n = 5). A considerable amount of variance in the rate and amount of the product, 3,4-dihydroxybenzoic acid (3,4-DHBA), was observed when one microdialysis probe was placed in the reaction mixture. When two microdialysis probes were placed in the reaction mixture, a greater rate and amount of 3,4-DHBA was observed. Different concentrations of 3,4-DHBA were obtained between quiescent and stirred systems.

Ascorbic Acid↗

Pharmacokinetics of different doses of methotrexate at steady state by in situ microdialysis in a rat model.

We used a microdialysis technique to monitor extracellular methotrexate (MTX) levels during the steady state in a rodent model. Microdialysis probes were implanted in the muscle, liver, and kidney of anesthetized male Wistar rats. MTX (18.75-500 mg/kg) was given as a continuous infusion through a venous catheter, and blood samples were obtained through a second venous catheter. Heparinized plasma, ultrafiltered plasma, microdialysis effluent from tissues, and tissue samples (obtained at the end of experiments) were analyzed for MTX content by high-performance liquid chromatography (HPLC). Steady state was demonstrated in the blood and tissues from 2 h until the end of the experiments (6 h). Extracellular drug levels in muscle and liver displayed a linear correlation with doses, whereas kidney levels reached a plateau at an MTX dose of 150 mg/kg per 6 h. Microdialysis-fluid endpoint levels for muscle, liver, and kidney were positively correlated to the endpoint total tissue levels (r2 = 0.80, 0.85, and 0.68, respectively). In the kidneys, the maximal relative tissue MTX accumulation was measured at a total dose of 75 mg/kg per 6 h. At higher doses, the relative drug sequestration declined to less than half of the values observed at this dose. This study demonstrates that the microdialysis technique can provide reproducible data on MTX tissue exposure in an animal model and that it offers a means of serial and reproducible monitoring of extracellular-tissue MTX levels at steady state and over a wide dose range. Pending additional studies, microdialysis may be a helpful technique for elucidating the kinetics of drug delivery to both targeted and toxicity-prone tissues during chemotherapy.

Animals↗

[Cerebral microdialysis in stroke].

Cerebral microdialysis is an invasive technique for neurochemical monitoring that has been established for neuro-critical disorders such as subarachnoid hemorrhage and severe brain injury. We present data on cerebral microdialysis in stroke patients which were obtained in an ongoing study supported by the German Ministry for Education and Research. So far, 50 patients have been included who required critical care due to massive stroke of the middle cerebral artery territory. By correlating the microdialysis results with follow-up CT scans, we could define the neurochemical characteristics of three different brain compartments: (1) noninfarcted brain tissue with normal microdialysis values, (2) brain areas adjacent to the infarct core which were not hypodense in CT scans but caused reversible neurochemical alterations, and (3) the infarct core with massive concentration changes which did not normalize over the measuring period of 3 to 5 days. Microdialysis values averaged over time and correlated with initial PET scans helped to describe neurochemical predictors of a malignant, i.e., life-threatening, space-occupying course of the ischemic stroke. We discuss the value of this method in guiding therapy and predicting clinical outcome in the context of other neurological critical care disorders and describe the pros and cons of cerebral microdialysis as an invasive monitoring technique.

Brain Edema↗

Continuous intratumoral microdialysis during high-dose methotrexate therapy in a patient with malignant fibrous histiocytoma of the femur: a case report.

We used a microdialysis technique to assay intratumoral methotrexate (MTX) levels during high-dose (12 g/m2 given as a 4-h infusion) therapy in a 43-year-old man with a malignant fibrous histiocytoma in the medial femoral condyle. Additional microdialysis probes were implanted in muscle tissue contralateral to the tumor and in an antecubital vein. Microdialysis was attempted during the initial two high-dose courses, but the two latter probes were removed at the start of the second treatment cycle due to leakage. No attempt to correct for microdialysis recovery was made. The intratumorally localized probe gave reproducible data on tumor MTX exposure of 9.3-14% of unbound systemic MTX. There was a close correlation between tumor and systemic levels for both MTX and its major extracellular metabolite 7-hydroxymethotrexate. Although limited to the study of MTX pharmacokinetics in a single subject, the experiment demonstrates that intratumoral microdialysis may provide data on tumor drug exposure, although of an indirect nature and dependent on the probe characteristics, the flow rate, and, possibly, the time after probe implantation. We propose that the application of microdialysis may prove useful for elucidation of the relationship between local drug exposure and the therapeutic response in normally inaccessible compartments during cancer pharmacotherapy.

Adult↗

[Clinical use of bedside cerebral microdialysis: a review].

OBJECTIVE: To review the current data on clinical bedside use of cerebral microdialysis. DATA SOURCE: Search through Medline database of articles in French and English (keywords: microdialysis, cerebral ischaemia, head trauma, subarachnoid haemorrhage, clinical study). STUDY SELECTION: All clinical articles published between 1995 and 2005, including original papers and some case reports. DATA SYNTHESIS: Microdialysis after occlusive stroke has shown elevated levels of glutamate and lactate. When space-occupying oedema develops, biochemistry abnormalities occur first, before ICP increases. Bedside microdialysis appears to be a sensitive and earlier indicator of space occupying oedema. Most Accurate markers to monitor ischaemia induced by vasospasm are glutamate and lactate/pyruvate ratio. These markers are earlier than clinical abnormalities or pressure measurements (sensibility 82%, specificity 89%). In the field of head trauma, the same compounds were utilised. The level of these compounds correlates with outcome in a different manner whether the area studied is close to a concussion or not. Most of biochemical events are linked to global cerebral ischaemia. We can observe some abnormalities limited to the pericontusional area, which are not detected by the global monitoring. Microdialysis appears a useful tool to investigate disease mechanisms but cannot be recommended for a widespread use after head trauma. CONCLUSION: Bedside cerebral microdialysis allows clinical decisions in the setting of subarachnoid haemorrhage and ischaemic stroke. It represents a valuable tool to investigate head trauma pathophysiology.

Biomarkers↗

Peritoneal microdialysis in freely moving rodents: an alternative to blood sampling for pharmacokinetic studies in the rat and the mouse.

By performing microdialysis in the peritoneal cavity, we studied the pharmacokinetics of Tramadol in awake, freely moving small laboratory animals. The systemic exposure to Tramadol was determined using both microdialysis sampling and collection of whole blood following a single intravenous injection (10 mg/kg) or a single oral dose (100 mg/kg) of Tramadol HCl. The sampling frequency of the dialysate was 10 min (mouse study) or 20 min (rat study). In rats and in mice, intraperitoneal microdialysis sampling gets reliable pharmacokinetic results without taking blood. The concentration-time curves obtained from peritoneal microdialysis were parallel to the concentration-time curves obtained from classical blood sampling. Accordingly, dose independent pharmacokinetic parameters were similar. A scaling factor, however, has to be introduced (e.g. peritoneal versus plasma AUC ratio) in order to obtain comparable pharmacokinetic results also with dose-dependent parameters. As there was no blood loss during the experiment, peritoneal microdialysis allowed the investigation of complete concentration-time curve profiles. Thus, the number of animals could be kept to a minimum. In conclusion, in vivo peritoneal microdialysis is a unique tool to obtain a complete set of free drug concentrations to determine reliable pharmacokinetic parameters from awake, freely moving rodents. Therefore, we suppose that the technique will have relevance for pharmacokinetic studies in future.

Administration, Oral↗

From artificial cerebro-spinal fluid (aCSF) to artificial extracellular fluid (aECF): microdialysis perfusate composition effects on in vivo brain ECF glucose measurements.

Microdialysis (mD) is the predominant technique for measurements of brain chemistry, especially when such measurements are made in awake animals. Relatively little attention has been paid, however, to the potential effect on such measurements of variation in the perfusate solution used. Here, we report that small variations in the ionic composition of microdialysis perfusate produced four-fold differences (0.53-2.18 mM) in the results obtained when measuring brain extracellular fluid (ECF) glucose. These changes may be linked to concomitant alterations of local neural activity caused by the perfusate composition. In addition to perfusate composition, probe type also proved to have a significant impact on microdialysis measurements. Further, we report the first direct microdialysis measurements of brain ECF ionic composition, showing significant differences from that of the cerebro-spinal fluid (CSF). Modifying the ionic composition of microdialysis perfusate based on these measurements resulted in a measured hippocampal ECF glucose level of 1.26 +/- .04 mM. Increased understanding of the impact of differences in the perfusate solutions used by different laboratories may provide a basis for reconciliation of apparently disparate microdialysis results within the literature.

Animals↗

Microdialysis of neuropeptide Y in human muscle tissue.

Microdialysis of neuropeptide Y (NPY) has been reported to be difficult, which partly may be due to the adhesive nature of the molecule. The aim of this study was to determine the optimal probe and perfusion medium for microdialysis of NPY and to investigate if microdialysis can be used to sample NPY from human muscle tissue. Three different probe types with a 10mm membrane were used for experiments in vitro. They were perfused with a modified Krebs-Henseleit buffer (KHB), with or without the addition of 0.5% human serum albumin (HSA). Dialysate samples were collected at different flow rates. Ten healthy subjects participated in the clinical microdialysis. Microdialysis samples were obtained by probes inserted intramuscularly in the right masseter and trapezius muscle and perfused with KHB+HSA at a flow-rate of 4 microl/min. The relative recovery of NPY was significantly higher in the dialysates with HSA added to the perfusion medium, while there was no difference between the three probe types. NPY was detectable in 90% of the dialysates from the masseter and in 40% of the dialysates from the trapezius muscle. In conclusion, this study shows that NPY can be detected in microdialysis samples from human skeletal muscle and that addition of HSA to the perfusion medium increases the relative recovery in vitro.

Adult↗