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Open Flow Microperfusion: An Alternative Method to Microdialysis?

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Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 4))

Abstract

Membrane-based sampling systems encounter problems when sampling high molecular weight or highly lipophilic substances in the interstitial fluid. Open flow microperfusion (OFM) overcomes these problems by replacing the membrane with a steel mesh featuring macroscopic openings in combination with a peristaltic OFM pump in push/pull mode to achieve stable recovery of OFM samples. Unfiltered sampling results in a complete representation of the ISF for relative and absolute quantification in the target tissue. Current applications in adipose subcutaneous tissue (aOFM) and dermal tissue (dOFM) range from preclinical studies to clinical trials, and cover a wide range of substances from small ions to lipophilic topical drugs to large antibodies. The latest development in OFM has been designed for use in cerebral tissue (cOFM). Currently used in preclinical research, cOFM allows effective sampling in brain tissue with an intact blood–brain barrier. Future work will combine OFM with metabolomics for a more complete assessment of metabolic pathways.

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References

  • Anderson CD (2006) Cutaneous microdialysis: is it worth the sweat? J Invest Dermatol 126:1207–1209

    Article  PubMed  CAS  Google Scholar 

  • Andlin-Sobocki P, Rössler W (2005) Cost of psychotic disorders in Europe. Eur J Neurol 12(Suppl 1):74–77

    Article  PubMed  Google Scholar 

  • Benfeldt E, Hansen SH, Vølund A et al (2007) Bioequivalence of topical formulations in humans: evaluation by dermal microdialysis sampling and the dermatopharmacokinetic method. J Invest Dermatol 127:170–178

    Article  PubMed  CAS  Google Scholar 

  • Benveniste H, Diemer NH (1987) Cellular reactions to implantation of a microdialysis tube in the rat hippocampus. Acta Neuropathol 74:234–238

    Article  PubMed  CAS  Google Scholar 

  • Benveniste H, Drejer J, Schousboe A, Diemer NH (1987) Regional cerebral glucose phosphorylation and blood flow after insertion of a microdialysis fiber through the dorsal hippocampus in the rat. J Neurochem 49:729–734

    Article  PubMed  CAS  Google Scholar 

  • Bodenlenz M, Höfferer C, Magnes C et al (2012) Dermal PK/PD of a lipophilic topical drug in psoriatic patients by continuous intradermal membrane-free sampling. Eur J Pharm Biopharm (in press)

    Google Scholar 

  • Bodenlenz M, Schaupp L, Druml T et al (2005) Measurement of interstitial insulin in human adipose and muscle tissue under moderate hyperinsulinemia by means of direct interstitial access. Am J Physiol Endocrinol Metab 289:296–300

    Article  Google Scholar 

  • Bos JD (2003) Non-steroidal topical immunomodulators provide skin-selective, self-limiting treatment in atopic dermatitis. Eur J Dermatol 13:455–461

    PubMed  CAS  Google Scholar 

  • Bungay PM, Newton-Vinson P, Isele W et al (2003) Microdialysis of dopamine interpreted with quantitative model incorporating probe implantation trauma. J Neurochem 86:932–946

    Article  PubMed  CAS  Google Scholar 

  • Chaurasia CS, Müller M, Bashaw ED et al (2007) AAPS-FDAFDA workshop white paper: microdialysis principles, application and regulatory perspectives. Pharm Res 24:1014–1025

    Article  PubMed  CAS  Google Scholar 

  • Clapp-Lilly KL, Roberts RC, Duffy LK et al (1999) An ultrastructural analysis of tissue surrounding a microdialysis probe. J Neurosci Methods 90:129–142

    Article  PubMed  CAS  Google Scholar 

  • Ellmerer M, Schaupp L, Brunner GA et al (2000) Measurement of interstitial albumin in human skeletal muscle and adipose tissue by open-flow microperfusion. Am J Physiol Endocrinol Metab 278:352–356

    Google Scholar 

  • Ellmerer M, Schaupp L, Sendlhofer G et al (1998a) Lactate metabolism of subcutaneous adipose tissue studied by open flow microperfusion. J Clin Endocrinol Metab 83:4394–4401

    Article  PubMed  CAS  Google Scholar 

  • Ellmerer M, Schaupp L, Trajanoski Z et al (1998b) Continuous measurement of subcutaneous lactate concentration during exercise by combining open-flow microperfusion and thin-film lactate sensors. Biosens Bioelectron 13:1007–1013

    Article  PubMed  CAS  Google Scholar 

  • Ferris WF, Crowther NJ (2011) Once fat was fat and that was that: our changing perspectives on adipose tissue. Cardiovasc J Afr 22:147–154

    Article  PubMed  CAS  Google Scholar 

  • Goldmann EE (1913) Vitalfärbung am Zentralnervensystem. In: Königliche Preußische Akademie der Wissenschaften. Verlag der Königlichen Akademie der Wissenschaften, Berlin, pp 1–13

    Google Scholar 

  • Grabb MC, Sciotti VM, Gidday JM et al (1998) Neurochemical and morphological responses to acutely and chronically implanted brain microdialysis probes. J Neurosci Methods 82:25–34

    Article  PubMed  CAS  Google Scholar 

  • Groothuis DR, Ward S, Schlageter KE et al (1998) Changes in blood-brain barrier permeability associated with insertion of brain cannulas and microdialysis probes. Brain Res 803:218–230

    Article  PubMed  CAS  Google Scholar 

  • Holmgaard R, Nielsen JB, Benfeldt E (2010) Microdialysis sampling for investigations of bioavailability and bioequivalence of topically administered drugs: current state and future perspectives. Skin Pharmacol Physiol 23:225–243

    Article  PubMed  CAS  Google Scholar 

  • Ikeoka D, Mader JK, Pieber TR (2010a) Adipose tissue, inflammation and cardiovascular disease. Rev Assoc Med Bras 56:116–121

    Article  PubMed  Google Scholar 

  • Ikeoka D, Pachler C, Korsatko S et al (2010b) Interleukin-6 produced in subcutaneous adipose tissue is linked to blood pressure control in septic patients. Cytokine 50:284–291

    Article  PubMed  CAS  Google Scholar 

  • Ikeoka DT, Pachler C, Mader JK et al (2011) Lipid-heparin infusion suppresses the IL-10 response to trauma in subcutaneous adipose tissue in humans. Obesity (Silver Spring) 19:715–721

    Article  CAS  Google Scholar 

  • IMS Retail Drug Monitor (2004) Health, (San Francisco), p 1–4

    Google Scholar 

  • Innovative Medicines Initiative (IMI) (2008) Creating Biomedical R&D Leadership for Europe to Benefit Patients and Society. 2008:118

    Google Scholar 

  • Jensen SM, Hansen HS, Johansen T, Malmlöf K (2007) In vivo and in vitro microdialysis sampling of free fatty acids. J Pharm Biomed Anal 43:1751–1756

    Article  PubMed  CAS  Google Scholar 

  • Kola I, Landis J (2004) Can the pharmaceutical industry reduce attrition rates? Nat Rev Drug Discov 3:711–715

    Article  PubMed  CAS  Google Scholar 

  • de Lange EC, Danhof M, de Boer AG, Breimer DD (1997) Methodological considerations of intracerebral microdialysis in pharmacokinetic studies on drug transport across the blood-brain barrier. Brain Res Rev 25:27–49

    Article  PubMed  Google Scholar 

  • Lindpointner S, Korsatko S, Köhler G et al (2010a) Use of the site of subcutaneous insulin administration for the measurement of glucose in patients with type 1 diabetes. Diabetes Care 33:595–601

    Article  PubMed  CAS  Google Scholar 

  • Lindpointner S, Korsatko S, Köhler G et al (2010b) Glucose levels at the site of subcutaneous insulin administration and their relationship to plasma levels. Diabetes Care 33:833–838

    Article  PubMed  CAS  Google Scholar 

  • Maggs DG, Jacob R, Rife F et al (1997) Counterregulation in peripheral tissues: effect of systemic hypoglycemia on levels of substrates and catecholamines in human skeletal muscle and adipose tissue. Diabetes 46:70–76

    Article  PubMed  CAS  Google Scholar 

  • Maggs DG, Jacob R, Rife F et al (1995) Interstitial fluid concentrations of glycerol, glucose, and amino acids in human quadricep muscle and adipose tissue. Evidence for significant lipolysis in skeletal muscle. J Clin Invest 96:370–377

    Article  PubMed  CAS  Google Scholar 

  • Manaenko A, Chen H, Kammer J et al (2011) Comparison Evans Blue injection routes: Intravenous versus intraperitoneal, for measurement of blood-brain barrier in a mice hemorrhage model. J Neurosci Methods 195:206–210

    Article  PubMed  Google Scholar 

  • Miller G (2002) Drug targeting. Breaking down barriers. Science (New York) 297:1116–1118

    Article  CAS  Google Scholar 

  • Müller M, Holmäng A, Andersson OK et al (1996) Measurement of interstitial muscle glucose and lactate concentrations during an oral glucose tolerance test. Am J Physiol 271:1003–1007

    Google Scholar 

  • Olesen J, Leonardi M (2003) The burden of brain diseases in Europe. Eur J Neurol 10:471–477

    Article  PubMed  CAS  Google Scholar 

  • Pachler C, Ikeoka D, Plank J et al (2007) Subcutaneous adipose tissue exerts proinflammatory cytokines after minimal trauma in humans. Am J Physiol Endocrinol Metab 293:690–696

    Article  Google Scholar 

  • Pardridge WM (2002) Drug and gene delivery to the brain: the vascular route. Neuron 36:555–558

    Article  PubMed  CAS  Google Scholar 

  • Pardridge WM (2005) The blood-brain barrier: bottleneck in brain drug development. Neuron 2:3–14

    Google Scholar 

  • Rosenbloom AJ, Ferris RL, Ferris R et al (2006) In vitro and in vivo protein sampling by combined microdialysis and ultrafiltration. J Immunol Methods 309:55–68

    Article  PubMed  CAS  Google Scholar 

  • Rosenbloom AJ, Sipe DM, Weedn VW (2005) Microdialysis of proteins: performance of the CMA/20 probe. J Neurosci Methods 148:147–153

    Article  PubMed  CAS  Google Scholar 

  • Schaupp L, Ellmerer M, Brunner GA et al (1999) Direct access to interstitial fluid in adipose tissue in humans by use of open-flow microperfusion. Am J Physiol 276:401–408

    Google Scholar 

  • Schmidt FJ, Sluiter WJ, Schoonen AJ (1993) Glucose concentration in subcutaneous extracellular space. Diabetes Care 16:695–700

    Article  PubMed  CAS  Google Scholar 

  • Sjögren F, Svensson C, Anderson C (2002) Technical prerequisites for in vivo microdialysis determination of interleukin-6 in human dermis. Br J Dermatol 146:375–382

    PubMed  Google Scholar 

  • Skrabal F, Trajanoski Z, Kontscheider H et al (1995) Portable system for on-line continuous ex vivo monitoring of subcutaneous tissue glucose using open tissue perfusion. Med Biol Eng 33:116–118

    Article  CAS  Google Scholar 

  • Stenken JA, Church MK, Gill CA, Clough GF (2010) How minimally invasive is microdialysis sampling? A cautionary note for cytokine collection in human skin and other clinical studies. The AAPS Journal 12:73–78

    Article  PubMed  CAS  Google Scholar 

  • Sternberg F, Meyerhoff C, Mennel FJ et al (1995) Subcutaneous glucose concentration in humans. Real estimation and continuous monitoring. Diabetes Care 18:1266–1269

    Article  PubMed  CAS  Google Scholar 

  • Trajanoski Z, Brunner GA, Schaupp L et al (1997) Open-flow microperfusion of subcutaneous adipose tissue for on-line continuous ex vivo measurement of glucose concentration. Diabetes Care 20:1114–1121

    Article  PubMed  CAS  Google Scholar 

  • Upton RN (2007) Cerebral uptake of drugs in humans. Clin Exp Pharmacol Physiol 34:695–701

    Article  PubMed  CAS  Google Scholar 

  • Westergren I, Nyström B, Hamberger A, Johansson BB (1995) Intracerebral dialysis and the blood-brain barrier. J Neurochem 64:229–234

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Frank Sinner .

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Pieber, T. et al. (2013). Open Flow Microperfusion: An Alternative Method to Microdialysis?. In: Müller, M. (eds) Microdialysis in Drug Development. AAPS Advances in the Pharmaceutical Sciences Series, vol 4. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-4815-0_15

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