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PubMed1999

Microdialysis: use in human exercise studies.

Microdialysis has been used for 25 years to study brain function in vivo. Recently, it has been developed for investigations on peripheral tissues. A microdialysis catheter is an artificial blood vessel system which can be placed in the extracellular space of various tissues such as adipose tissue and skeletal muscle in order to examine these tissues in situ. Molecules are collected from the tissue by the device and their true interstitial concentration can be estimated. Metabolically-active molecules can be delivered to the interstitial space through the microdialysis probe and their action on the tissue can be investigated locally without producing generalized effects. It is also possible to study local tissue blood flow with microdialysis by adding a flow marker (usually ethanol) to the microdialysis solvent. The microdialysis technique is particularly useful for studies of small and water-soluble molecules. A number of important observations on the in vivo regulation of lipolysis, carbohydrate metabolism and blood flow in human skeletal muscle and adipose tissue have been made recently using microdialysis.

Adipose Tissue↗
PubMed1997

Application of microdialysis in pharmacokinetic studies.

The objective of this review is to survey the recent literature regarding the various applications of microdialysis in pharmacokinetics. Microdialysis is a relatively new technique for sampling tissue extracellular fluid that is gaining popularity in pharmacokinetic and pharmacodynamic studies, both in experimental animals and humans. The first part of this review discusses various aspects of the technique with regard to its use in pharmacokinetic studies, such as: quantitation of the microdialysis probe relative recovery, interfacing the sampling technique with analytical instrumentation, and consideration of repeated procedures using the microdialysis probe. The remainder of the review is devoted to a survey of the recent literature concerning pharmacokinetic studies that apply the microdialysis sampling technique. While the majority of the pharmacokinetic studies that have utilized microdialysis have been done in the central nervous system, a growing number of applications are being found in a variety of peripheral tissue types, e.g. skin, muscle, adipose, eye, lung, liver, and blood, and these are considered as well. Given the rising interest in this technique, and the ongoing attempts to adapt it to pharmacokinetic studies, it is clear that microdialysis sampling will have an important place in studying drug disposition and metabolism.

Animals↗
PubMed1994

Microdialysis: an alternative for in vitro and in vivo protein binding studies.

The aim of the present study was to compare the performance of conventional equilibrium dialysis method with a microdialysis method in studying drug protein binding. The two methods were assessed by comparing the measured mean unbound drug fraction in different plasma species in vitro in plasma of four different species and at two concentrations of the non-indolic melatonin analog S 20098. For the microdialysis study, the unbound drug fraction was calculated after correction for membrane recovery. Plasma protein binding of S 20098 ranged from 75 to 95%. In humans, rabbits and rats (10 ng/ml), equal unbound percentages were found between equilibrium dialysis and microdialysis. Microdialysis gave slightly but significantly higher values in rat (2000 ng/ml), and in monkey plasma independent of the drug concentration. Microdialysis was also performed in vivo in freely moving rats under steady-state conditions, yielding similar unbound fraction values (26.0 +/- 0.9%) to those obtained using microdialysis probes in rat plasma in vitro (24.4 +/- 1.6%). These results support the use of in vivo microdialysis in pharmacokinetic studies in freely moving animals.

Acetamides↗
PubMed2002

Validation of microdialysis sampling for oral availability studies by means of a new ganciclovir prodrug.

Microdialysis sampling was validated for oral availability studies using ganciclovir (9-(1, 3-dihydroxy-2-propoxymethyl) guanine) and a ganciclovir prodrug (9-(1-L-valyloxy-3-octadecanoyloxy-prop-2-oxymethyl) guanine). Three different techniques were used in the study; microdialysis, blood and urinesampling. The oral uptake (11+/-2%) and the urinary recovery (106+/-5%) were determined. Animals given ganciclovir subcutaneously were subject either to microdialysis and blood sampling or to microdialysis alone. There was no significant difference between microdialysis and blood sampling in terms of blood concentration data, CL, Vd, half-life or AUC by means of Student's t-test. The oral bioavailability of the prodrug was 40+/-7% estimated from microdialysis sampling data and 48+/-4% estimated from urine sampling data. It is concluded that microdialysis is a valid method to use in pharmacokinetic studies of oral availability as well as for basic pharmacokinetic parameter estimation.

Administration, Oral↗
PubMed1999

Enhanced microdialysis recovery of some tricyclic antidepressants and structurally related drugs by cyclodextrin-mediated transport.

The enhanced microdialysis relative recovery (RR) of some hydrophobic tricyclic drugs (imipramine, desipramine, amitriptyline, carbamazepine and promethazine) is discussed. Enhanced RR was achieved by including a binding agent [beta-cyclodextrin (beta-CD) or 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD)] in the microdialysis perfusion fluid to form inclusion complexes with the drugs, which increases the analyte flux through the membrane material. The maximum effect of the RR increase for all the drugs studied was observed using a commercially available polycarbonate-polyether (PC) membrane. With a 4 mm PC membrane and 4.41 mmol l-1 (0.5% w/v) beta-CD included in the microdialysis perfusion fluid (0.9% saline, pH 7.4) at a flow rate of 0.5 microliter min-1, RR enhancements over controls were as follows: carbamazepine 136, imipramine 268, desipramine 298, amitriptyline 634, and promethazine 987%. Increasing beta-CD [up to 17.63 mmol l-1 (2% w/v)] or HP-beta-CD [up to 32.5 mmol l-1 (5% w/v)] concentration in the microdialysis perfusion fluid enhanced carbamazepine RR three (beta-CD) to four (HP-beta-CD) times compared to controls through PC microdialysis membranes. The PC membrane gave enhanced RR values that were twice those for cuprophan or AN-69 membranes. Enhanced RR with cyclodextrins was successfully applied to sampling from a protein solution containing desipramine in a 4% w/v bovine serum albumin solution. These results suggest that addition of cyclodextrins to microdialysis perfusion fluids may be used to increase microdialysis RR during blood sampling.

Antidepressive Agents, Tricyclic↗
PubMedDate not supplied

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.

Animals↗
PubMed2003

Microdialysis of dopamine interpreted with quantitative model incorporating probe implantation trauma.

Although microdialysis is widely used to sample endogenous and exogenous substances in vivo, interpretation of the results obtained by this technique remains controversial. The goal of the present study was to examine recent criticism of microdialysis in the specific case of dopamine (DA) measurements in the brain extracellular microenvironment. The apparent steady-state basal extracellular concentration and extraction fraction of DA were determined in anesthetized rat striatum by the concentration difference (no-net-flux) microdialysis technique. A rate constant for extracellular clearance of DA calculated from the extraction fraction was smaller than the previously determined estimate by fast-scan cyclic voltammetry for cellular uptake of DA. Because the relatively small size of the voltammetric microsensor produces little tissue damage, the discrepancy between the uptake rate constants may be a consequence of trauma from microdialysis probe implantation. The trauma layer has previously been identified by histology and proposed to distort measurements of extracellular DA levels by the no-net-flux method. To address this issue, an existing quantitative mathematical model for microdialysis was modified to incorporate a traumatized tissue layer interposed between the probe and surrounding normal tissue. The tissue layers are hypothesized to differ in their rates of neurotransmitter release and uptake. A post-implantation traumatized layer with reduced uptake and no release can reconcile the discrepancy between DA uptake measured by microdialysis and voltammetry. The model predicts that this trauma layer would cause the DA extraction fraction obtained from microdialysis in vivo calibration techniques, such as no-net-flux, to differ from the DA relative recovery and lead to an underestimation of the DA extracellular concentration in the surrounding normal tissue.

Animals↗
PubMed1999

Distribution to the skin of penciclovir after oral famciclovir administration in healthy volunteers: comparison of the suction blister technique and cutaneous microdialysis.

Penciclovir is a drug active against herpes simplex viruses located in the epidermis basal layer. The aim of this study was to compare the suction blister technique and microdialysis as methods to measure the penciclovir concentration in the skin after a single dose (250 mg) of its prodrug, famciclovir. Suction blister fluid, microdialysates and plasma were sampled from 11 healthy volunteers for 5 h after famciclovir administration. Both the suction blister technique and microdialysis showed that penciclovir reaches the skin in concentrations sufficient to inhibit herpes virus replication. The maximum concentration in both suction blister fluid and in microdialysate was observed later than in plasma. The microdialysis concentration was decreased by cooling of the skin surface and by adrenaline-mediated vasoconstriction. The microdialysis recovery of penciclovir was studied with respect to the flow-rate of perfusion medium through the microdialysis probe. Microdialysis and the suction blister technique can be used to study the time-concentration profile of penciclovir in the skin and microdialysis allows a continuous sampling of the drug for a prolonged time after administration.

2-Aminopurine↗
PubMed1997

Microdialysis in the human brain: review of its applications.

The analysis of brain extracellular fluid can provide essential information about both the physiology and the pathology of the human nervous system. The introduction of microdialysis into the clinical sciences has provided a new opportunity to study this environment. Using microdialysis, endogenous substances can be obtained and drugs can be delivered in very close proximity to the receptors and ion channels on neuronal membranes. In this sense, microdialysis can be regarded as a novel technique since it can continuously measure interstitial brain activity in living tissue while causing minimal adverse effects. Although it has been well established as an experimental technique for neurochemistry, the true utility of microdialysis as a clinical tool is still being defined. The potential clinical applications of microdialysis to characterize the human brain extracellular environment in patients with pathologic conditions has grown rapidly. The number of publications in which microdialysis has been performed in clinical studies has been increasing during recent years and this article gives a summary of those reports where microdialysis was applied in the study of human brain disorders.

Brain↗
PubMed1997

Microdialysis studies of the role of chemical agents in secondary damage upon spinal cord injury.

Assorted microdialysis studies of the roles endogenous chemical agents may play in secondary damage upon spinal cord injury (SCI) are described. Issues addressed include the concentrations reached upon injury, mechanisms of release upon injury, and effects of drugs on injury-elicited increases in glutamate concentrations. An important question in identifying an agent of secondary damage upon central nervous system (CNS) trauma is not simply whether the substance is released upon injury, but whether it reaches harmful levels. To resolve this requires establishing the concentration attained and then determining whether administering that level damages neurons. To make microdialysis measurements of amino acids in the CNS more quantitative, we characterized the effects of insertion of a microdialysis fiber on leakage of glutamate from the circulation and explored the effects of depletion by microdialysis on release caused by SCI. Very high glutamate concentrations were found around the fiber for several hours after fiber insertion and 2 days later, and there was substantial leakage of alpha-aminoisobutyric acid from the circulation into the dialysis zone for several hours after fiber insertion. Glutamate concentrations reached upon SCI under nondepleting conditions were similar to those estimated earlier under depleting conditions. Mg2+ release was detectable when microdialysis probes were perfused with Mg2+-free fluid, but not when the concentrations in the perfusing fluid approximated those in the interstitial space. It is concluded (1) that insertion of microdialysis probes into CNS tissue can cause long-lasting leakage of amino acids from the circulation into the space around the fiber, (2) that this leakage can obscure concentration changes that otherwise occur, and (3) that depletion of substances in the fluid around the fiber may cause increases in concentration to be observed that do not normally happen. We also describe demonstrations that administration of methylprednisolone and dihydrokainic acid diminish increases in glutamate concentrations caused by SCI, showing that microdialysis can be used to explore effects of drugs on actions of damaging substances.

Animals↗
PubMed2006

Intensive insulin therapy reduces microdialysis glucose values without altering glucose utilization or improving the lactate/pyruvate ratio after traumatic brain injury.

OBJECTIVE: To determine that intensive glycemic control does not reduce microdialysis glucose concentration brain metabolism of glucose. DESIGN: Prospective monitoring followed by retrospective data analysis of cerebral microdialysis and global brain metabolism. SETTING: Single center, academic neurointensive care unit. PATIENTS: Forty-seven moderate to severe traumatic brain injury patients. INTERVENTIONS: A nonrandomized, consecutive design was used for glycemic control with loose insulin (n=33) for the initial 2 yrs or intensive insulin therapy (n=14) for the last year. MEASUREMENTS AND MAIN RESULTS: In 14 patients treated with intensive insulin therapy, there was a reduction in microdialysis glucose by 70% of baseline concentration compared with a 15% reduction in 33 patients treated with a loose insulin protocol. Despite this reduction in microdialysis glucose, the global metabolic rate of glucose did not change. However, intensive insulin therapy was associated with increased incidence of microdialysis markers of cellular distress, namely elevated glutamate (38+/-37% vs. 10+/-17%, p<.01), elevated lactate/pyruvate ratio (38+/-37% vs. 19+/-26%, p<.03) and low glucose (26+/-17% vs. 11+/-15%, p<.05, and increased global oxygen extraction fraction. Mortality was similar in the intensive and loose insulin treatment groups (14% vs. 15%, p=.9), as was 6-month clinical outcome (p=.3). CONCLUSIONS: Intensive insulin therapy results in a net reduction in microdialysis glucose and an increase in microdialysis glutamate and lactate/pyruvate without conveying a functional outcome advantage.

Adult↗
PubMed2006

Microdialysis in clinical practice: monitoring intraoral free flaps.

Clinical examination is still the gold standard of postoperative free flap monitoring, but with intraorally situated and/or buried flaps, it can be difficult or impossible. Microdialysis is a sampling technique which offers the possibility to monitor the metabolism of a flap continuously. Ischemia can be detected by monitoring the changes in glucose, lactate, and pyruvate levels in interstitial fluid of the specific tissue. Our aim was to use microdialysis to monitor the metabolism of free flaps used for reconstructions inside the oral cavity/oropharynx and to evaluate the reliability and usefulness of this new monitoring method.Twenty-five consecutive patients who underwent oral cavity/oropharynx cancer resection and immediate reconstruction with free flap were included in the study. A microdialysis catheter was placed into the subcutaneous adipose tissue of the flap in the end of the surgical procedure. Dialysate samples were taken on an hourly basis for 72 hours postoperatively. Routine clinical monitoring was carried out by experienced nursing staff. Clinical findings were recorded and later compared with microdialysis values. Two flaps out of 25 failed in spite of reoperations. In both problem cases, microdialysis indicated ischemia 1 to 2 hours before it became clinically evident. During flap ischemia, the lactate/pyruvate ratio increased, glucose concentrations reduced, whereas lactate level increased when compared with normal values. Our results indicate that microdialysis is safe for the patient and the flap. It can reliably detect flap ischemia at an early stage. This is especially useful in buried flaps when clinical monitoring is difficult. Microdialysis may also reduce the patient discomfort caused by repeated clinical examination of the flap.

Adult↗
PubMed2005

Microdialysis for measurement of hepatic and systemic nitric oxide biosynthesis in septic rats.

BACKGROUND: We sought to compare two techniques, microdialysis and repeated blood withdrawal, for serial assessment of hepatic and systemic nitric oxide (NO) biosynthesis in septic rats. METHODS: Rats were randomly allocated to either microdialysis or blood withdrawal groups. Two microdialysis probes, one in liver and the other in right atrium, were placed in rats in the microdialysis group. Half of the rats from each group were then given lipopolysaccharide (LPS) to induce NO production. The other half of the rats from each group were injected with vehicle (normal saline) to serve as controls. In the microdialysis group, dialysate (30 microl) was collected every 30 min. In the blood withdrawal group, 0.3 ml of blood was drawn every 30 min. Sampling was performed up to 6 h after injection of LPS or vehicle. Hemodynamics, hepatic and systemic NO concentrations, and iNOS expression in harvested liver tissues were assayed. RESULTS: Repeated blood withdrawal by itself caused a significant decrease in blood pressure and induced hepatic iNOS expression. Microdialysis, on the contrary, reliably detected LPS-induced NO production without resulting either in hemodynamic changes or in iNOS induction in liver tissue. CONCLUSIONS: Microdialysis provides serial measure of hepatic and systemic NO concentrations in LPS-treated rats without the need for removal of tissue.

Animals↗
PubMed1994

Intracerebral microdialysis combined with recording of extracellular field potential: a novel method for investigation of depolarizing drugs in vivo.

1. The purpose of this study was to examine whether depolarizations evoked by excitatory amino acids can be recorded quantitatively, in vivo, with a microelectrode incorporated within a microdialysis probe. 2. Microdialysis probes incorporating a chlorided silver wire were implanted in the striatum of anaesthetized rats and perfused with artificial cerebrospinal fluid (ACSF). Increasing concentrations of excitatory amino acids were applied for 2 min via the microdialysis probe, and the extracellular direct current (d.c.) potential was recorded between the microdialysis electrode and a reference electrode placed under the scalp. 3. N-methyl-D-aspartate (NMDA, 25-500 microM), alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA, 5-1000 microM), kainate (5-500 microM), and glutamate (0.25-100 mM) evoked concentration-dependent depolarizations with maxima ranging from 7 to 10 mV, i.e. 3 to 10 times larger than those recorded from brain slices in vitro. Depolarizations evoked by glutamate receptor agonists applied by microdialysis shared several features with those recorded from brain slices. The most characteristic were: steep onset and recovery of NMDA and glutamate responses; marked post-depolarization hyperpolarization with NMDA; and very slow recovery after kainate application. At high concentrations (500 microM), NMDA occasionally initiated spreading depression. The relative potency of glutamate and NMDA was of the same order of magnitude to that obtained with the cortical wedge and hippocampal slices, glutamate being 100 to 400 times less potent than NMDA. 4. Two consecutive series of NMDA-stimuli within the same procedure evoked comparable depolarizations, indicating that reliable quantitative analysis of drug action can be performed, with each animal serving as its own control. This is relevant to the study of drugs acting on glutamate receptors especially antagonists. The remarkable inter-animal reproducibility is also a valuable feature.5. Pretreatment with dizocilpine maleate (MK-801, 2mgkg'1, i.p.) reduced by 65% the responses evoked by NMDA (500 fM). The non-NMDA antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX,100 1M) applied via the microdialysis probe reduced by around 78% the responses to AMPA and kainate (250 micro M). The fact that drugs, especially antagonists, can be administered either systemically, or directly through the dialysis probe to by-pass the blood-brain barrier or avoid peripheral effects, is especially relevant for neuropharmacological studies.6. Intracerebral microdialysis combined with in vivo recording of extracellular field potential is a novel and valuable method for the quantitative analysis of the action of drugs acting on glutamate receptors.This method should prove especially useful for comparing the sensitivity of specific brain structures to selective glutamate receptor agonists under normal conditions and when the neuronal micro environment is altered. It should also be useful for investigating the action of other depolarizing agents, such as veratridine, and their antagonists.

Animals↗
PubMed1996

Microdialysis for metabolic monitoring in neonates after surgery.

Microdialysis is a new method for continuous metabolic monitoring. We studied the possibility of using microdialysis in neonates treated in a paediatric intensive care unit after surgery. A microdialysis catheter was inserted in the abdominal subcutaneous adipose tissue in 14 neonates for a median of 93 h (range 24-106 h). In four neonates, two microdialysis catheters were used simultaneously. Samples were taken hourly for analysis of glucose, lactate and glycerol. Dialysate and blood concentrations were compared. Serum/whole blood glucose values (n = 68) were in the range 2.1-15.4 mM. The serum glucose levels showed good agreement with the dialysate concentrations of glucose, although these infants were subjected to various forms of stress, drugs and glucose infusions. The whole blood glucose levels were significantly lower than the dialysate levels. The microdialysis concentrations of glucose varied considerably. As almost identical dialysate glucose levels were found when two microdialysis catheters were used simultaneously, the variability probably reflects true changes in blood glucose levels. Our results indicate that microdialysis can be used in neonates.

Anal Canal↗
PubMed1994

In vivo microdialysis for the transdermal absorption of valproate in rats.

The suitability of sampling via microdialysis for a lipophilic drug, valproate (VPA), was evaluated by the elimination rate constant of VPA solution in an in vitro experimental first-order elimination system. The elimination rate constant of VPA in dialysate was found to be 0.43 +/- 0.05h-1, which was in good agreement with the real elimination rate constant (0.46 +/- 0.02h-1). A change in VPA concentration in the solution surrounding a microdialysis probe was well maintained by the microdialysis method, suggesting no adsorption between the membrane of the microdialysis probe and VPA. On the basis of the in vitro experiment, the effect of a penetration enhancer, 1-[2-(decylthio)ethyl]azacyclopentan-2-one (HPE-101), on the transdermal absorption of VPA was examined in rats by the use of microdialysis in vivo. An intradermal microdialysis was performed at a flow rate of 1.0 microliter/min for 7h after the dermal application of 50 mM VPA solution with or without 3% (w/v) HPE-101. HPE-101 increased the transdermal absorption rate of VPA by 80 times compared with the control. The microdialysis system was found to be quite useful for assessing the in vivo transdermal absorption of a lipophilic VPA.

Animals↗
PubMed1994

In vivo microdialysis for pharmacokinetic investigations: a plasma protein binding study of valproate in rabbits.

The use of microdialysis to study the binding of valproate (VPA) to plasma proteins was evaluated in rabbits. Prior to an in vivo microdialysis, in vitro relative recovery of VPA respectively from Ringer's solution, 5% (w/v) of albumin solution and plasma sample via a microdialysis probe was examined. The in vitro relative recovery was defined as a ratio of the VPA concentration determined in the dialysate to the free VPA concentration in the sample solution surrounding the membrane of the microdialysis probe. When the sample solution was well stirred at 700 rpm and maintained at 37 degrees C, the in vitro relative recovery of VPA was significantly different among them. It increased in the order of Ringer's solution (34.3 +/- 2.6%) > 5% (w/v) of albumin solution (25.7 +/- 4.6%) > rabbit plasma sample (15.8 +/- 1.2%). Thereafter, pharmacokinetics of VPA was determined using both microdialysis sampling via the rabbit femoral vein and collection of whole blood via the rabbit ear vein after intravenous administration of VPA at a dose of 43 mg/kg. Free concentrations of VPA in plasma were determined by ultrafiltration method as opposed to microdialysis method. There was no difference in the elimination half-life of VPA determined by microdialysis, 1.09 +/- 0.22 h, or ultrafiltration, 1.22 +/- 0.21 h. The AUC of VPA in dialysate was 15 +/- 4 micrograms.h/ml, which corresponded to 15% of that in ultrafiltrate (103 +/- 17 micrograms.h/ml). The value was in good agreement with the in vitro relative recovery of VPA from plasma sample (15.8 +/- 1.2%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2005

Microdialysis: current applications in clinical pharmacokinetic studies and its potential role in the future.

Microdialysis is a probe-based sampling method, which, if linked to analytical devices, allows for the measurement of drug concentration profiles in selected tissues. During the last two decades, microdialysis has become increasingly popular for preclinical and clinical pharmacokinetic studies. The advantage of in vivo microdialysis over traditional methods relates to its ability to continuously sample the unbound drug fraction in the interstitial space fluid (ISF). This is of particular importance because the ISF may be regarded as the actual target compartment for many drugs, e.g. antimicrobial agents or other drugs mediating their action through surface receptors. In contrast, plasma concentrations are increasingly recognised as inadequately predicting tissue drug concentrations and therapeutic success in many patient populations. Thus, the minimally invasive microdialysis technique has evolved into an important tool for the direct assessment of drug concentrations at the site of drug delivery in virtually all tissues. In particular, concentrations of transdermally applied drugs, neurotransmitters, antibacterials, cytotoxic agents, hormones, large molecules such as cytokines and proteins, and many other compounds were described by means of microdialysis. The combined use of microdialysis with non-invasive imaging methods such as positron emission tomography and single photon emission tomography opened the window to exactly explore and describe the fate and pharmacokinetics of a drug in the body. Linking pharmacokinetic data from the ISF to pharmacodynamic information appears to be a straightforward approach to predicting drug action and therapeutic success, and may be used for decision making for adequate drug administration and dosing regimens. Hence, microdialysis is nowadays used in clinical studies to test new drug candidates that are in the pharmaceutical industry drug development pipeline.

Animals↗