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PubMed1996

In-vivo microdialysis study of extracellular glutamate response to temperature variance in subarachnoid hemorrhage.

Neurochemical changes may precede the development of clinical signs in neurological disease. Early identification of such changes may offer an opportunity to avoid or treat complications. Under experimental conditions, extracellular levels of glutamate and other amino acids can be monitored by in-vivo microdialysis in cerebral ischemia, head trauma and epilepsy. Data on the release of glutamate under ischemic conditions in humans are limited. There is no published data on the effects of temperature variation or other manipulations on the extracellular glutamate levels in humans. We report for the first time, the effects of changes in temperature on the extracellular cerebral glutamate levels as measured by in-vivo microdialysis, the dialysate being collected before, during and after cooling in four patients with subarachnoid hemorrhage. Three of the patients had in-vivo microdialysis carried out postoperatively. One patient underwent microdialysis three days prior to the surgical clipping of the aneurysm. In all patients, mild head cooling resulted in a significant decrease in extracellular glutamate levels. The effect of cooling was most apparent when the extracellular glutamate concentrations were high. In two patients, the extracellular glutamate levels increased sharply with fever but returned to normal once the temperature normalized. In vivo microdialysis can be used to measure extracellular glutamate and other neurotransmitters with minimal discomfort in awake humans. This technique offers a unique opportunity to monitor the neurochemistry in critically ill patients and it may aid in developing therapeutic intervention strategies to minimize undesired chemical responses.

Cold Temperature↗
PubMed1994

Increase of basic fibroblast growth factor (bFGF, FGF-2) messenger RNA and protein following implantation of a microdialysis probe into rat hippocampus.

In vivo microdialysis is an established tool for sampling extracellular fluid compartments. However, microdialysis faces the problem that the implantation of the probe damages the microenvironment from which measurements are derived. In this study, we examined the expression of basic fibroblast growth factor mRNA and protein at the cellular level after implantation of a microdialysis probe into the dorsal hippocampus and found that 8 h after inserting the probe bFGF mRNA was markedly increased in a relatively large area centered around the probe, involving both the dorsal hippocampus and the overlying cerebral cortex, as revealed by radioactive in situ hybridization. Using nonradioactive in situ hybridization with digoxigenin-labelled riboprobes, combined with immunohistochemistry for glial fibrillary acidic protein we demonstrated that bFGF mRNA was exclusively increased in astrocytes at the probe insertion site. Using immunohistochemistry we also found that bFGF-like immunoreactivity was increased after implantation of the probe close to the lesion site, as shown by an increased number of bFGF immunoreactive nuclear glial profiles. These results provide evidence that the implantation of a microdialysis probe into the brain induces activation of bFGF gene expression in astrocytes associated with nuclear bFGF-like immunoreactivity. We conclude that lesion-induced effects have to be considered when evaluating microdialysis data, and that mechanical trauma to the brain will activate astroglial trophism, as seen from the increased density of astroglial profiles demonstrating bFGF mRNA and protein levels.

Animals↗
PubMed1999

Consequences of static and pulsatile pressure on transmembrane exchanges during in vitro microdialysis: implication for studies in cardiac physiology.

Microdialysis is an established technique for measuring the kinetics of various neurotransmitters within the extracellular space in the field of neurochemistry. Recently, its use has been extended to sampling in other tissues, including liver, kidney and the heart. A persistent problem in cardiac microdialysis concerns two parameters related to myocardial function: pressure and frequency (heart rate). The aim of the study is to evaluate the consequences of pressure and frequency on transmembrane exchanges. Linear flexible microdialysis probes (membrane length: 12 mm, outside diameter: 390 microns, MWCO 50,000 Daltons) were designed in our laboratory. The probes, perfused at 2 microL/min with sterile water, were placed in a system filled with a glucose solution (2 g/L) and able to generate either static: 0 to 400 mmHg (0 to 53.31 kPa) or pulsatile pressure: 0-100; 0-200; 0-300 mmHg (0-13.32; 0-26.65; 0-39.98 kPa) at different frequencies: 1, 2 and 3 Hz. At 2 mu litre min-1 perfusion rate, the pressure inside the probe is estimated to be 80 mmHg (10.66 kPa). Under static pressure conditions, the glucose recovery rate can be expressed as an exponential function, and the outflow rate can be expressed as a linear function of the external pressure level. Under dynamic conditions, the external mean pressure must be accounted for. When external mean pressure exceeds 80 mmHg (10.66 kPa) (pressure generated by the flow rate of perfusion inside the probe), the recovery rate increases with frequency. Conversely, if the outer mean pressure is lower than 80 mmHg (10.66 kPa), the recovery rate decreases with frequency. Theoretical and experimental modelling results in a nomogram that can be used to estimate in vivo recovery. In conclusion, mass transfer across a microdialysis membrane is dependent on the direction of the transmembrane pressure gradient and increases with heart rate. These findings must be taken into account when in vivo recovery rates during cardiac microdialysis are determined.

Calibration↗
PubMed2006

Microdialysis as a tool in local pharmacodynamics.

In many cases the clinical outcome of therapy needs to be determined by the drug concentration in the tissue compartment in which the pharmacological effect occurs rather than in the plasma. Microdialysis is an in vivo technique that allows direct measurement of unbound tissue concentrations and permits monitoring of the biochemical and physiological effects of drugs throughout the body. Microdialysis was first used in pharmacodynamic research to study neurotransmission, and this remains its most common application in the field. In this review, we give an overview of the principles, techniques, and applications of microdialysis in pharmacodynamic studies of local physiological events, including measurement of endogenous substances such as acetylcholine, catecholamines, serotonin, amino acids, peptides, glucose, lactate, glycerol, and hormones. Microdialysis coupled with systemic drug administration also permits the more intensive examination of the pharmacotherapeutic effect of drugs on extracellular levels of endogenous substances in peripheral compartments and blood. Selected examples of the physiological effects and mechanisms of action of drugs are also discussed, as are the advantages and limitations of this method. It is concluded that microdialysis is a reliable technique for the measurement of local events, which makes it an attractive tool for local pharmacodynamic research.

Acetylcholine↗
PubMed2004

Myocardial redox state during coronary artery bypass grafting assessed with microdialysis.

PURPOSE: Microdialysis allows the biochemical analysis of interstitial fluids of nearly every organ as a bedside procedure. This technique could be useful to reveal data about the myocardial metabolism during cardiopulmonary bypass in human coronary artery bypass graft (CABG) surgery. METHODS: In 17 patients undergoing CABG a myocardial microdialysis catheter (CMA 70, CMA/Microdialysis AB, Sweden) was inserted in the apical region of the beating heart. Microdialysis measurements were performed at timed intervals before, during, and after cardiopulmonary bypass (CPB). The concentrations of lactate and pyruvate were analyzed semi-continuously. RESULTS: During CPB the myocardial lactate-pyruvate-ratio (LPR) rose from an initial 11 (8-15) to 33 (29-41) ( P<0.01). After CPB the LPR decreased to 4 (3-7) at the end of observation ( P<0.05). The pyruvate concentration showed an immediate increase from 34 (30-42) microM at the end of CPB to 181 (147-234) microM after removal of the cross-clamp with subsequent increase during reperfusion ( P<0.01). Plasma lactate and pyruvate showed no essential changes during the study. CONCLUSION: Using the microdialysis technique it was possible to analyze myocardial metabolic changes during CABG. The course of myocardial LPR as a sensitive indicator of the myocardial redox state showed profound changes during and after CPB. We propose the microdialysis technique as an additional monitoring tool in CABG.

Aged↗
PubMed2004

Consensus meeting on microdialysis in neurointensive care.

BACKGROUND: Microdialysis is used in many European neurointensive care units to monitor brain chemistry in patients suffering subarachnoid hemorrhage (SAH) or traumatic brain injury (TBI). DISCUSSION: We present a consensus agreement achieved at a meeting in Stockholm by a group of experienced users of microdialysis in neurointensive care, defining the use of microdialysis, placement of catheters, unreliable values, chemical markers, and clinical use in SAH and in TBI. CONCLUSIONS: As microdialysis is maturing into a clinically useful technique for early detection of cerebral ischemia and secondary brain damage, there is a need to following such definition regarding when and how to use microdialysis after SAH and TBI.

Brain Injuries↗
PubMed2003

Detection of intestinal ischemia using a microdialysis technique in an animal model.

The purpose of this study was to use a microdialysis technique to demonstrate the metabolic changes that occur in the intestinal wall during ischemia in vivo. Continuous monitoring of glucose, lactate, and glycerol using a microdialysis technique was performed in the jejunal wall of 10 pigs during steady-state and occlusive ischemia. The microdialysis catheters were introduced 50, 80, and 110 cm from the ligament of Treitz. Occlusive ischemia was established to two segments after steady state was reached. Microdialysate samples were collected from ischemic/nonischemic intestinal segments simultaneously every 20 minutes. For comparison with the microdialysis measurements, systemic blood samples were drawn from the cannulated femoral artery and analyzed consecutively. A significant increase of microdialysate lactate and a significant decrease of microdialysate glucose were found during occlusive ischemia as compared to the preischemic samples and samples from the nonischemic control catheters. The microdialysate glycerol increased during ischemia, but later than the lactate. No changes were observed in systemic serum lactate, serum glucose, pH, p co(2), and p o(2), but serum potassium increased by 1.1 mmole (median) during ischemia. Microdialysis measured in the intestinal wall identifies local ischemia and may be a new method for the monitoring of intestinal perfusion.

Animals↗
PubMed1996

Determination of extracellular methotrexate tissue levels by microdialysis in a rat model.

We used a microdialysis technique to determine tissue methotrexate (MTX) levels during steady state in a rodent model. Two different approaches were employed to measure the actual extracellular MTX concentrations in muscle, liver, and kidney tissues of anesthetized Wistar rats. With the reduced-perfusion-rate technique, the flow in the microdialysis perfusate was gradually decreased toward zero to permit calculation of zero-flow intercepts. Using the net change technique, microdialysis probes were perfused with different MTX concentrations to allow an assessment of equilibrium drug levels. For these two methods to be used, drug concentrations in the matrix to be analyzed must remain unchanged during the experimental procedure. In the animal model, steady state was attained after 1.5 h and maintained throughout the rest of the experiments by the administration of MTX as continuous infusions through a venous catheter. In vitro and in vivo, both the reduced-perfusion-rate and net change techniques gave reproducible data that permitted the estimation of extracellular drug concentrations in the dialyzed tissue compartments.The data suggest that the level of unbound MTX in the circulation is fairly similar to the extracellular concentrations in the muscle and liver. In the kidney, MTX levels were measured to be 3-8 times higher than those of unbound, circulating MTX, and a considerable discrepancy between the two methods used for estimations was apparent. These results demonstrate that both the net change and reduced-flow microdialysis techniques can produce reproducible and precise data. The results may constitute a basis for determining recoveries and, thus, true extracellular drug levels during in vivo microdialysis of MTX. This may be of importance in delineation of the relationship between tissue MTX levels and outcome in a variety of normally inaccessible compartments during cancer pharmacotherapy.

Animals↗
PubMed1999

Effect of barrier perturbation on cutaneous penetration of salicylic acid in hairless rats: in vivo pharmacokinetics using microdialysis and non-invasive quantification of barrier function.

The penetration of topically applied drugs is altered in diseased or barrier-damaged skin. We used microdialysis in the dermis to measure salicylic acid (SA) penetration in hairless rats following application to normal (unmodified) skin (n = 11) or skin with perturbed barrier function from (1) tape-stripping (n = 5), (2) sodium lauryl sulphate (SLS) 2% for 24 h (n = 3) or (3) delipidization by acetone (n = 4). Prior to the experiment, transepidermal water loss (TEWL) and erythema were measured. Two microdialysis probes were inserted into the dermis on the side of the trunk and 5% SA in ethanol was applied in a chamber overlying the probes. Microdialysis sampling was continued for 4 h, followed by measurements of probe depth by ultrasound scanning. SA was detectable in all samples and rapidly increasing up to 130 min. Microdialysates collected between 80 and 200 min showed mean SA concentrations of 3 microg/ml in unmodified and acetone-treated skin, whereas mean SA concentrations were 280 microg/ml in SLS-pretreated skin and 530 microg/ml in tape-stripped skin (P < 0.001). The penetration of SA correlated with barrier perturbation measured by TEWL (P < 0.001) and erythema (P < 0.001). A correlation between dermal probe depth and SA concentration was found in unmodified skin (P = 0.04). Microdialysis sampling in anatomical regions remote from the dosed site excluded the possibility that SA levels measured were due to systemic absorption. Microdialysis sampling of cutaneous penetration was highly reproducible. Impaired barrier function, caused by irritant dermatitis or tape stripping, resulted in an 80- to 170-fold increase in the drug level in the dermis. This dramatic increase in drug penetration could be relevant to humans, in particular to topical treatment of skin diseases and to occupational toxicology.

Absorption↗
PubMed2001

Determination of amino acid tissue concentrations by microdialysis: method evaluation and relation to plasma values.

Microdialysis is an in vivo technique to monitor tissue concentrations of low molecular weight substances by means of a continuously perfused artificial capillary with a semipermeable membrane placed into the region of interest. The suitability of microdialysis to determine tissue concentrations of amino acids was evaluated in vitro by placing the catheter into Ringer buffer or into a plasma protein (50g/l) solution containing 32 different amino acids (150 micromol/l each). All amino acids tested crossed freely the microdialysis membrane with recoveries close to 100%. Microdialysis fluid was sampled from subcutaneous tissue of five newborns and amino acid content analysed. Total and non protein bound amino acids were determined in the patients plasma by acid precipitation or ultrafiltration, respectively. Mean subcutaneous tissue concentrations were lower as compared to plasma for taurine, serine, alanine, aspartate, glutamate and ornithine and higher for valine, isoleucine, leucine, methionine, phenylalanine, tyrosine and arginine, indicating net uptake or release of amino acids from subcutaneous tissue. Thus, microdialysis offers a convenient and minimal invasive way to study tissue amino acid composition and appears to be a promising analytical tool for the study of amino acid metabolism in vivo.

Amino Acids↗
PubMed1995

Application of microdialysis to clinical pharmacokinetics in humans.

OBJECTIVE: Measurement of drug concentrations in tissues would be useful for clinical pharmacokinetic studies, but appropriate experimental methods are not available at present. The aim of this study was to assess the scope and limitations of the microdialysis technique for human tissue pharmacokinetic studies. METHODS: Microdialysis probes were inserted into the medial vastus muscle or the periumbilical subcutaneous adipose layer of 13 healthy volunteers. Thereafter, volunteers received either acetaminophen (paracetamol, 1000 mg orally) or gentamicin (160 mg, intravenous bolus). Drug concentrations were monitored in plasma, muscle, and subcutaneous tissue. Calibration of the microdialysis probes was carried out in vitro and in vivo with use of the retrodialysis method. RESULTS: For both model compounds, complete concentration versus time profiles in muscle and subcutaneous tissue could be obtained. Major pharmacokinetic parameters (absorption half-life, elimination half-life, maximum concentration, time to reach maximum concentration, area under the curve, and area under the inhibitory curve) were calculated for tissues; tissue/plasma concentration ratios could be derived. Reproducibility of tissue drug concentration measurements was high. CONCLUSIONS: We have shown that microdialysis sampling is a suitable tool for measuring drug concentrations in human muscle and subcutaneous tissues. Microdialysis is readily applicable, relatively noninvasive, and reproducible. This technique may become a valuable addition for pharmacokinetic characterization of selected drugs.

Acetaminophen↗
PubMed1994

Microdialysis sampling in tumor and muscle: study of the disposition of 3-amino-1,2,4-benzotriazine-1,4-di-N-oxide (SR 4233).

Microdialysis sampling was used to study the pharmacokinetics and disposition of SR 4233 (3-amino-1,2,4-benzotriazine-1,4-di-N-oxide), a representative of a new class of bioreductive antineoplastic agents. The pharmacokinetics of unbound SR 4233 in plasma was determined using a flexible microdialysis probe implanted into the jugular vein of conscious, freely-moving rats. No difference in the plasma pharmacokinetics was observed between healthy and tumor bearing rats. In both cases a biexponential decay following an i.v. dose was observed with t1/2 (alpha) of 13.4 +/- 3.2 minutes and t1/2 (beta) of 37.0 +/- 14.4 minutes. Binding of SR 4233 to plasma proteins was determined to be concentration independent at 21.4 +/- 2.9%. A linear microdialysis probe was used to sample solid tumor and muscle tissue in vivo to study the disposition of SR 4233 into these tissues. Similar elimination kinetics were observed in both tissues although the peak concentration of SR 4233 in muscle was 20 times that in the tumor. The extent of reductive metabolism was much greater in the tumor relative to muscle. This was observed after both a systemic dose of SR 4233 and direct dosing to the tissue through the microdialysis probe. This study demonstrates the potential of microdialysis sampling in vivo to the study of the disposition of drugs.

Animals↗
PubMed1994

Simultaneous single-cell recording and microdialysis within the same brain site in freely behaving rats: a novel neurobiological method.

We present a method for performing intracerebral microdialysis in freely behaving rats while recording the firing of neurons within the dialysis site. Studying hippocampal theta cells and complex-spike cells with this technique, it has been found that: (1) when the microdialysis fluid contained only artificial cerebrospinal fluid, both types of neurons displayed normal electrical activity, (2) the simultaneous single-cell recording/microdialysis procedure could be readily performed for as long as 3 days, and (3) inclusion of drugs into the microdialysis fluid, at appropriate concentrations, caused clear changes in firing pattern. For example, microdialysis with 1% lidocaine completely abolished, whereas that with 50 mM K+ markedly increased, the neuronal electrical activity. These cellular changes developed without apparent EEG or behavioral manifestations and were reversible. In some of the experiments, the extracellular concentrations of glutamate and aspartate in the recording/dialysis site were also measured. The described method allows the extracellular environment of recorded brain cells to be manipulated by drugs delivered through the microdialysis probe and simultaneously allows determination of the neurochemical composition of that environment over a remarkably long period of time and in intact, physiologically functioning, neural network. Such studies will provide new insights into the molecular basis of neuronal activity in the brain in the context of behavior, including learning.

Animals↗
PubMed2006

Natural and synthetic affinity agents as microdialysis sampling mass transport enhancers: current progress and future perspectives.

Microdialysis sampling is a diffusion-based separation method that allows analytes to freely diffuse across a hollow fiber semi-permeable dialysis membrane. This sampling technique has been widely used for in vivo chemical collection. The inclusion of affinity-based trapping agents into the microdialysis perfusion fluid serves to improve the relative recovery via the binding reaction of low molecular weight hydrophobic analytes and larger analytes such as peptides and proteins. Here, we briefly review our past studies using different compounds (native cyclodextrins and antibodies) to improve microdialysis sampling recovery. A brief compilation of our studies using antibody-immobilized beads as a means to improve cytokine collection during microdialysis sampling is also described. We present new work focused on the use of antibody-immobilized bead microdialysis sampling enhancement for various endocrine hormones (amylin, GLP-1, glucagon, insulin, and leptin). The antibody-bead enhancement approach allowed for recovery enhancements that ranged between 3 and 20-fold for these peptides. Using the enhanced recovery approach, endocrine peptides at pM concentrations can be quantified. Finally, our initial work focused on developing non-antibody based enhancement agents using bovine serum albumin-heparin conjugates covalently bound to polystyrene microspheres is presented for the cytokine, tumor necrosis factor-alpha (TNF-alpha). Unlike antibodies, heparin provides the advantage of being reusable as an enhancement agent and served to improve the relative recovery of TNF-alpha by three-fold.

Biosensing Techniques↗
PubMed2005

Measurement of glucose and metabolites in subcutaneous adipose tissue during hyperglycemia with microdialysis at various perfusion flow rates.

BACKGROUND: Microdialysis-based glucose sensors have recently been introduced for monitoring glucose levels in diabetic patients. The flow rate by which the fluid sample is pumped through the microdialysis catheter varies in different studies. AIM: To study the effects of various flow rates on glucose and its metabolites sampled by microdialysis during an oral glucose tolerance test. MATERIAL, METHODS: Glucose, lactate, pyruvate and glycerol were measured with microdialysis in interstitial fluid of subcutaneous adipose tissue in twelve healthy young subjects before and during an oral glucose tolerance test using four different flow rates (0.3, 1, 2 and 5 microL/min) and a 30 mm dialysis membrane. RESULTS: At the basal fasting state the dialysate glucose obtained by 0.3 microL/min was equal to capillary glucose concentration. A decrease in dialysate glucose levels during the basal state was observed for higher flow rates but not for 0.3 microL/min, which indicates a depleting effect. The relative increase after OGTT was similar for capillary glucose and flow rate 0.3 microL/min but not for higher flow rates. CONCLUSION: The low microdialysis flow rate (0.3 microL/min) facilitates the capture of true interstitial glucose concentrations during glucose fluctuations. Thus this low flow rate is preferred in studies of local tissue metabolism.

Adipose Tissue↗
PubMed2004

Insulin stimulated glucose disposal in peripheral tissues studied with microdialysis and stable isotope tracers.

BACKGROUND & AIMS: Methods to study glucose kinetics in vivo in specific tissues or tissue beds in humans are often not feasible due to invasiveness or costs of equipment needed. Here we investigate whether the loss (fractional extraction) of 2H7-glucose infused via a microdialysis catheter can be used to study glucose disposal in skeletal muscle and subcutaneous adipose tissue. METHODS AND RESULTS: A perfusion period of 2 h was needed to ensure an isotopic steady state in the microdialysis catheters in skeletal muscle and adipose tissue. In six healthy volunteers the fractional extraction increased during a hyperinsulinemic euglycemic clamp in both skeletal muscle and adipose tissue. Following 48 h of starvation in the same subjects, insulin was not able to increase the fractional extraction of 2H7-glucose from the microdialysis in comparison with a baseline measurement. CONCLUSIONS: In response to insulin infusion, the fractional extraction of 2H7-glucose from a microdialysis catheter increases in skeletal muscle and subcutaneous adipose tissue and this increase is blunted during insulin resistance induced by starvation. These results validate that the fractional extraction of a glucose tracers infused via microdialysis can be used as an index of glucose disposal in peripheral tissues or tissue beds.

Adipose Tissue↗
PubMed2005

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.

Animals↗
PubMed2006

Cochlear microdialysis for quantification of dexamethasone and fluorescein entry into scala tympani during round window administration.

Before new drugs for the treatment of inner ear disorders can be studied in controlled clinical trials, it is important that their pharmacokinetics be established in inner ear fluids. Microdialysis allows drug levels to be measured in perilymph without the volume disturbances and potential cerebrospinal fluid contamination associated with fluid sampling. The aims of this study were to show: (i) that despite low recovery rates from miniature dialysis probes, significant amounts of drug are removed from small fluid compartments, (ii) that dialysis sampling artifacts can be accounted for using computer simulations and (iii) that microdialysis allows quantification of the entry rates through the round window membrane (RWM) into scala tympani (ST). Initial experiments used microdialysis probes in small compartments in vitro containing sodium fluorescein. Stable concentrations were observed in large compartments (1000 microl) but significant concentration declines were observed in smaller compartments (100, 10 and 5.6 microl) comparable to the size of the inner ear. Computer simulations of these experiments closely approximated the experimental data. In in vivo experiments, sodium fluorescein 10 mg/ml and dexamethasone-dihydrogen-phosphate disodium salt 8 mg/ml were simultaneously applied to the RWM of guinea pigs. Perilymph concentration in the basal turn of ST was monitored using microdialysis. The fluorescein concentration reached after 200 min application (585+/-527 microg/ml) was approximately twice that of dexamethasone phosphate (291+/-369 microg/ml). Substantial variation in concentrations was found between animals by approximately a factor of 34 for fluorescein and at least 41 for dexamethasone phosphate. This is, to a large extent, thought to be the result of the RWM permeability varying in different animals. It was not caused by substance analysis variations, because two different analytic methods were used and the concentration ratio between the two substances remained nearly constant across the experiments and because differences were apparent for the repeated samples obtained in each animal. Interpretation of the results using computer simulations allowed RWM permeability to be quantified. It also demonstrated, however, that cochlear clearance values could not be reliably obtained with microdialysis because of the significant contribution of dialysis to clearance. The observed interanimal variation, e.g., in RWM permeability, is likely to be clinically relevant to the local application of drugs in patients.

Animals↗