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Published in: Clinical Pharmacokinetics 3/2014

01-03-2014 | Review Article

Role of Microdialysis in Pharmacokinetics and Pharmacodynamics: Current Status and Future Directions

Authors: Francine Johansson Azeredo, Teresa Dalla Costa, Hartmut Derendorf

Published in: Clinical Pharmacokinetics | Issue 3/2014

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Abstract

Diagnostic and therapeutic decisions in medical practice are still generally based on blood concentrations of drugs and/or biomolecules despite the knowledge that biochemical events and pharmacological effects usually take place in tissue rather than in the bloodstream. Microdialysis is a semi-invasive technique that is able to measure concentrations of the free, active drug or endogenous compounds in almost all human tissues and organs. It is currently being used to monitor brain metabolic processes and quantify tissue biomarkers, and determine transdermal drug distribution and tissue pharmacokinetics, confirming its importance as a widely used sampling technique in clinical drug monitoring and drug development as well as therapy and disease follow-up, contributing to rationalizing drug dosing regimens and influencing the clinical decision-making process.
Literature
1.
go back to reference Ungerstedt U, Pycock C. Functional correlates of dopamine neurotransmission. Bull Schweiz Akad Med Wiss. 1974;30:44–55.PubMed Ungerstedt U, Pycock C. Functional correlates of dopamine neurotransmission. Bull Schweiz Akad Med Wiss. 1974;30:44–55.PubMed
2.
go back to reference Plock N, Kloft C. Microdialysis—theoretical background and recent implementation in applied life-sciences. Eur J Pharm Sci. 2005;25:1–24.CrossRef Plock N, Kloft C. Microdialysis—theoretical background and recent implementation in applied life-sciences. Eur J Pharm Sci. 2005;25:1–24.CrossRef
3.
go back to reference Muller M, De La Pena A, Derendorf H. Issues in pharmacokinetics and pharmacodynamics of anti-infective agents: distribution in tissue. Antimicrob Agents Chemother. 2004;48:1441–53.CrossRef Muller M, De La Pena A, Derendorf H. Issues in pharmacokinetics and pharmacodynamics of anti-infective agents: distribution in tissue. Antimicrob Agents Chemother. 2004;48:1441–53.CrossRef
4.
go back to reference Johanssen MJ, Newman RA, Madden T. The use of microdialysis in pharmacokinetic and pharmacodynamic. Pharmacotherapy. 1997;17(3):464–81. Johanssen MJ, Newman RA, Madden T. The use of microdialysis in pharmacokinetic and pharmacodynamic. Pharmacotherapy. 1997;17(3):464–81.
5.
go back to reference Chaurasia C, Müller M, Bashaw ED, et al. AAPS-FDA workshop white paper: microdialysis principles, application, and regulatory perspectives. J Clin Pharmacol. 2007;47:589–603.CrossRef Chaurasia C, Müller M, Bashaw ED, et al. AAPS-FDA workshop white paper: microdialysis principles, application, and regulatory perspectives. J Clin Pharmacol. 2007;47:589–603.CrossRef
6.
go back to reference Ryan DM. Pharmacokinetics of antibiotics in natural and experimental superficial compartments in animals and humans. Antimicrob Chemother. 1993;31 Suppl. D:1–16.CrossRef Ryan DM. Pharmacokinetics of antibiotics in natural and experimental superficial compartments in animals and humans. Antimicrob Chemother. 1993;31 Suppl. D:1–16.CrossRef
7.
go back to reference Huse DM, Schulman K, Orsini L, et al. Burden of illness in Parkinson’s disease. Mov Disord. 2005;20:1449–54.CrossRef Huse DM, Schulman K, Orsini L, et al. Burden of illness in Parkinson’s disease. Mov Disord. 2005;20:1449–54.CrossRef
8.
go back to reference Hillered L, Vespa PM, Hovda DA. Translational neurochemical research in acute human brain injury: the current status and potential future for cerebral microdialysis. J Neurotrauma. 2005;22(1):3–41.CrossRef Hillered L, Vespa PM, Hovda DA. Translational neurochemical research in acute human brain injury: the current status and potential future for cerebral microdialysis. J Neurotrauma. 2005;22(1):3–41.CrossRef
9.
go back to reference Brunner M, Derendorf H. Clinical microdialysis: current applications and potential use in drug development. Trends Anal Chem. 2006;25(7):674–80.CrossRef Brunner M, Derendorf H. Clinical microdialysis: current applications and potential use in drug development. Trends Anal Chem. 2006;25(7):674–80.CrossRef
10.
go back to reference Joukhadar C, Mueller M. Microdialysis: current applications in clinical pharmacokinetic studies and its potential role in the future. Clin Pharmacokinet. 2005;44(9):895–913.CrossRef Joukhadar C, Mueller M. Microdialysis: current applications in clinical pharmacokinetic studies and its potential role in the future. Clin Pharmacokinet. 2005;44(9):895–913.CrossRef
11.
go back to reference Carrel T, Schmid ER, von Segesser L, et al. Perioperative assessment of the likelihood of infection of the lower respiratory tract after cardiac surgery. Thorac Cardiovasc Surg. 1991;39:85–8.CrossRef Carrel T, Schmid ER, von Segesser L, et al. Perioperative assessment of the likelihood of infection of the lower respiratory tract after cardiac surgery. Thorac Cardiovasc Surg. 1991;39:85–8.CrossRef
12.
go back to reference Brunner M, Pernersdorfer T, Mayer B, et al. Surgery and intensive care procedures affect the target site distribution of piperacillin. Crit Care Med. 2000;28:1754–9.CrossRef Brunner M, Pernersdorfer T, Mayer B, et al. Surgery and intensive care procedures affect the target site distribution of piperacillin. Crit Care Med. 2000;28:1754–9.CrossRef
13.
go back to reference Joukhadar C, Frossard M, Mayer BX, et al. Impaired target site penetration of beta-lactams may account for therapeutic failure in patients with septic shock. Crit Care Med. 2001;29:385–91.CrossRef Joukhadar C, Frossard M, Mayer BX, et al. Impaired target site penetration of beta-lactams may account for therapeutic failure in patients with septic shock. Crit Care Med. 2001;29:385–91.CrossRef
14.
go back to reference Hyatt JM, McKinnon PS, Zimmer GS, et al. The importance of pharmacokinetic/pharmacodynamics surrogate markers to outcome: focus on antibacterial agents. Clin Pharmacokinet. 1995;28:143–60.CrossRef Hyatt JM, McKinnon PS, Zimmer GS, et al. The importance of pharmacokinetic/pharmacodynamics surrogate markers to outcome: focus on antibacterial agents. Clin Pharmacokinet. 1995;28:143–60.CrossRef
15.
go back to reference Theuretzbacher U. Tissue penetration of antibacterial agents: how should this be incorporated into pharmacodynamic analyses? Curr Opin Pharmacol. 2007;7:498–504.CrossRef Theuretzbacher U. Tissue penetration of antibacterial agents: how should this be incorporated into pharmacodynamic analyses? Curr Opin Pharmacol. 2007;7:498–504.CrossRef
16.
go back to reference Mouton JW, Theuretzbacher U, Craig WA, et al. Tissue concentrations: do we ever learn? J Antimicrob Chemother. 2008;61:235–7.CrossRef Mouton JW, Theuretzbacher U, Craig WA, et al. Tissue concentrations: do we ever learn? J Antimicrob Chemother. 2008;61:235–7.CrossRef
17.
go back to reference Traunmueller F, Zeitlinger M, Zeleny P, et al. Pharmacokinetics of single- and multiple-dose oral clarithromycin in soft tissues determined by microdialysis. Antmicrob Agents Chemother. 2007;519(9):3185–9.CrossRef Traunmueller F, Zeitlinger M, Zeleny P, et al. Pharmacokinetics of single- and multiple-dose oral clarithromycin in soft tissues determined by microdialysis. Antmicrob Agents Chemother. 2007;519(9):3185–9.CrossRef
18.
go back to reference Hutschala D, Skhirtladze K, Kinstner C, et al. In vivo microdialysis to measure antibiotic penetration into soft tissue during cardiac surgery. Ann Thorac Surg. 2007;84:1605–10.CrossRef Hutschala D, Skhirtladze K, Kinstner C, et al. In vivo microdialysis to measure antibiotic penetration into soft tissue during cardiac surgery. Ann Thorac Surg. 2007;84:1605–10.CrossRef
19.
go back to reference Barbour A, Schmidt S, Rout RW, et al. Soft tissue penetration of cefuroxime determined by clinical microdialysis in morbidly obese patients undergoing abdominal surgery. Int J Antimicrob Agents. 2009;34:231–5.CrossRef Barbour A, Schmidt S, Rout RW, et al. Soft tissue penetration of cefuroxime determined by clinical microdialysis in morbidly obese patients undergoing abdominal surgery. Int J Antimicrob Agents. 2009;34:231–5.CrossRef
20.
go back to reference Hutschala D, Kinstner C, Skhirtladze K, et al. The impact of perioperative atelectasis on antibiotic penetration into lung tissue: an in vivo microdialysis study. J Intensive Care Med. 2008;34:1827–34.CrossRef Hutschala D, Kinstner C, Skhirtladze K, et al. The impact of perioperative atelectasis on antibiotic penetration into lung tissue: an in vivo microdialysis study. J Intensive Care Med. 2008;34:1827–34.CrossRef
21.
go back to reference Poeppl W, Zeitlinger M, Donath O, et al. Penetration of doripenem in human brain: an observational microdialysis study in patients with acute brain injury. Int J Antimicrob Agents. 2012;39:343–5.CrossRef Poeppl W, Zeitlinger M, Donath O, et al. Penetration of doripenem in human brain: an observational microdialysis study in patients with acute brain injury. Int J Antimicrob Agents. 2012;39:343–5.CrossRef
22.
go back to reference Schmidt S, Barbour A, Sahre M, et al. PK/PD: new insights for antibacterial and antiviral applications. Curr Opin Pharmacol. 2008;8:549–56.CrossRef Schmidt S, Barbour A, Sahre M, et al. PK/PD: new insights for antibacterial and antiviral applications. Curr Opin Pharmacol. 2008;8:549–56.CrossRef
23.
go back to reference Jain RK. Delivery of molecular medicine to solid tumors. Science. 1996;271(5252):1079–80.CrossRef Jain RK. Delivery of molecular medicine to solid tumors. Science. 1996;271(5252):1079–80.CrossRef
24.
go back to reference Zamboni WC, Houghton PJ, Hulstein JL, et al. Interpatient variability in bioavailability and pharmacokinetics of oral topotecan in children with relapsed solid tumors. Cancer Chemother Pharmacol. 1999;43:269–76.CrossRef Zamboni WC, Houghton PJ, Hulstein JL, et al. Interpatient variability in bioavailability and pharmacokinetics of oral topotecan in children with relapsed solid tumors. Cancer Chemother Pharmacol. 1999;43:269–76.CrossRef
25.
go back to reference Brunner M, Muller M. Microdialysis: an in vivo approach for measuring drug delivery in oncology. Eur J Clin Pharmacol. 2002;58(4):227–34.CrossRef Brunner M, Muller M. Microdialysis: an in vivo approach for measuring drug delivery in oncology. Eur J Clin Pharmacol. 2002;58(4):227–34.CrossRef
26.
go back to reference Konings IR, Engels FK, Sleijfer S, et al. Application of prolonged microdialysis sampling in carboplatin-treated cancer patients. Cancer Chemother Pharmacol. 2009;64:509–16.CrossRef Konings IR, Engels FK, Sleijfer S, et al. Application of prolonged microdialysis sampling in carboplatin-treated cancer patients. Cancer Chemother Pharmacol. 2009;64:509–16.CrossRef
27.
go back to reference Konings IR, Sleijfer S, Mathijssen RH, et al. Increasing tumoral 5-fluorouracil concentrations during a 5-day continuous infusion: a microdialysis study. Cancer Chemother Pharmacol. 2011;67(5):1055–62.CrossRef Konings IR, Sleijfer S, Mathijssen RH, et al. Increasing tumoral 5-fluorouracil concentrations during a 5-day continuous infusion: a microdialysis study. Cancer Chemother Pharmacol. 2011;67(5):1055–62.CrossRef
28.
go back to reference Motl S, Zhuang Y, Waters CM, et al. Pharmacokinetic considerations in the treatment of CNS tumours. Clin Pharmacokinet. 2006;45:871–903.CrossRef Motl S, Zhuang Y, Waters CM, et al. Pharmacokinetic considerations in the treatment of CNS tumours. Clin Pharmacokinet. 2006;45:871–903.CrossRef
29.
go back to reference Cecchelli R, Berezowski V, Lundquist S, et al. Modelling of the blood-brain barrier in drug discovery, development. Nat Rev Drug Discov. 2007;6:650–61.CrossRef Cecchelli R, Berezowski V, Lundquist S, et al. Modelling of the blood-brain barrier in drug discovery, development. Nat Rev Drug Discov. 2007;6:650–61.CrossRef
30.
go back to reference Abbott N. Prediction of blood-brain barrier permeation in drug discovery from in vivo, in vitro, in silico models. Drug Discov Today Technol. 2004;1:407–16.CrossRef Abbott N. Prediction of blood-brain barrier permeation in drug discovery from in vivo, in vitro, in silico models. Drug Discov Today Technol. 2004;1:407–16.CrossRef
31.
go back to reference Muldoon LL, Soussain C, Jahnke K, et al. Chemotherapy delivery issues in central nervous system malignancy: a reality check. J Clin Oncol. 2007;25:2295–305.CrossRef Muldoon LL, Soussain C, Jahnke K, et al. Chemotherapy delivery issues in central nervous system malignancy: a reality check. J Clin Oncol. 2007;25:2295–305.CrossRef
32.
go back to reference Collins J, Dedrick R. Distributed model for drug delivery to CSF and brain tissue. Am J Physiol Regul Integr Comp Physiol. 1983;245(3):R303–10.CrossRef Collins J, Dedrick R. Distributed model for drug delivery to CSF and brain tissue. Am J Physiol Regul Integr Comp Physiol. 1983;245(3):R303–10.CrossRef
33.
go back to reference de Lange E, Danhof M. Considerations in the use of cerebrospinal fluid pharmacokinetics to predict brain target concentrations in the clinical setting: implications of the barriers between blood and brain. Clin Pharmacokinet. 2002;41(10):691–703.CrossRef de Lange E, Danhof M. Considerations in the use of cerebrospinal fluid pharmacokinetics to predict brain target concentrations in the clinical setting: implications of the barriers between blood and brain. Clin Pharmacokinet. 2002;41(10):691–703.CrossRef
34.
go back to reference Blakeley JO, Olson J, Grossman SA, et al. Effect of blood brain barrier permeability in recurrent high grade gliomas on the intratumoral pharmacokinetics of methotrexate: a microdialysis study. J Neurooncol. 2009;91:51–8.CrossRef Blakeley JO, Olson J, Grossman SA, et al. Effect of blood brain barrier permeability in recurrent high grade gliomas on the intratumoral pharmacokinetics of methotrexate: a microdialysis study. J Neurooncol. 2009;91:51–8.CrossRef
35.
go back to reference Portnow J, Badie B, Chen M, et al. The neuropharmacokinetics of temozolomide in patients with resectable brain tumors: potential implication for the current approach to chemoradiation. Clin Cancer Res. 2009;15:7092–8.CrossRef Portnow J, Badie B, Chen M, et al. The neuropharmacokinetics of temozolomide in patients with resectable brain tumors: potential implication for the current approach to chemoradiation. Clin Cancer Res. 2009;15:7092–8.CrossRef
36.
go back to reference Shah VP. Progress in methodologies for evaluating bioequivalence of topical formulations. Am J Clin Dermatol. 2001;2(5):275–80.CrossRef Shah VP. Progress in methodologies for evaluating bioequivalence of topical formulations. Am J Clin Dermatol. 2001;2(5):275–80.CrossRef
37.
go back to reference Au WL, Skinner MF, Benfeldt E, et al. Application of dermal microdialysis for the determination of bioavailability of clobetasol propionate applied to the skin of human subjects. Skin Pharmacol Physiol. 2012;25:17–24.CrossRef Au WL, Skinner MF, Benfeldt E, et al. Application of dermal microdialysis for the determination of bioavailability of clobetasol propionate applied to the skin of human subjects. Skin Pharmacol Physiol. 2012;25:17–24.CrossRef
38.
go back to reference Ortiz PG, Hansen SH, Shah VP, et al. Are marketed topical metronidazole creams bioequivalent? Evaluation by in vivo microdialysis sampling and tape stripping methodology. Skin Pharmacol Physiol. 2011;24:44–53.CrossRef Ortiz PG, Hansen SH, Shah VP, et al. Are marketed topical metronidazole creams bioequivalent? Evaluation by in vivo microdialysis sampling and tape stripping methodology. Skin Pharmacol Physiol. 2011;24:44–53.CrossRef
39.
go back to reference Tettey-Amlalo RNO, Kanfer I, Skinner MF, et al. Application of dermal microdialysis for the evaluation of bioequivalence of a ketoprofen topical gel. Eur J Pharm Sci. 2009;36:219–25.CrossRef Tettey-Amlalo RNO, Kanfer I, Skinner MF, et al. Application of dermal microdialysis for the evaluation of bioequivalence of a ketoprofen topical gel. Eur J Pharm Sci. 2009;36:219–25.CrossRef
40.
go back to reference Brunner M, Davies D, Martin W, et al. A new topical formulation enhances relative diclofenac bioavailability in healthy male subjects. Br J Clin Pharmacol. 2011;71(6):852–9.CrossRef Brunner M, Davies D, Martin W, et al. A new topical formulation enhances relative diclofenac bioavailability in healthy male subjects. Br J Clin Pharmacol. 2011;71(6):852–9.CrossRef
41.
go back to reference Simmel F, Kirbs C, Erdogan Z, et al. Pilot investigation on long-term subcutaneous microdialysis: proof of principle in humans. AAPS J. 2013;15(1):95–103.CrossRef Simmel F, Kirbs C, Erdogan Z, et al. Pilot investigation on long-term subcutaneous microdialysis: proof of principle in humans. AAPS J. 2013;15(1):95–103.CrossRef
42.
go back to reference Ortiz PG, Hansen SH, Shah VP, et al. Impact of adult atopic dermatitis on topical drug penetration: assessment by cutaneous microdialysis and tape stripping. Acta Derm Venereol. 2009;89:33–8.CrossRef Ortiz PG, Hansen SH, Shah VP, et al. Impact of adult atopic dermatitis on topical drug penetration: assessment by cutaneous microdialysis and tape stripping. Acta Derm Venereol. 2009;89:33–8.CrossRef
43.
go back to reference Ortiz PG, Hansen SH, Shah VP, et al. The effect of irritant dermatitis on cutaneous bioavailability of a metronidazole formulation investigated by microdialysis and dermatopharmacokinetic methods. Cont Derm. 2008;59(1):23–30.CrossRef Ortiz PG, Hansen SH, Shah VP, et al. The effect of irritant dermatitis on cutaneous bioavailability of a metronidazole formulation investigated by microdialysis and dermatopharmacokinetic methods. Cont Derm. 2008;59(1):23–30.CrossRef
44.
go back to reference Lonnroth P, Jansson PA, Smith U. A microdialysis method allowing characterization of intercellular water space in humans. Am J Physiol. 1987;253(2 Pt 1):E228–31.PubMed Lonnroth P, Jansson PA, Smith U. A microdialysis method allowing characterization of intercellular water space in humans. Am J Physiol. 1987;253(2 Pt 1):E228–31.PubMed
45.
go back to reference Blin O, Audebert C, Pitel S, et al. Effects of dimethylaminoethanol pyroglutamate (DMAE p-Glu) against memory deficits induced by scopolamine: evidence from preclinical and clinical studies. Psychopharmacology. 2009;207:201–12.CrossRef Blin O, Audebert C, Pitel S, et al. Effects of dimethylaminoethanol pyroglutamate (DMAE p-Glu) against memory deficits induced by scopolamine: evidence from preclinical and clinical studies. Psychopharmacology. 2009;207:201–12.CrossRef
46.
go back to reference Olivecrona M, Rodling-Wahlstrom M, Naredi S, et al. Prostacyclin treatment in severe traumatic brain injury: a microdialysis and outcome study. J Neurotrauma. 2009;26:1251–62.CrossRef Olivecrona M, Rodling-Wahlstrom M, Naredi S, et al. Prostacyclin treatment in severe traumatic brain injury: a microdialysis and outcome study. J Neurotrauma. 2009;26:1251–62.CrossRef
47.
go back to reference Brody DL, Magnoni S, Schwetye KE, et al. Amyloid-β dynamics correlate with neurological status in the injured human brain. Science. 2008;321(5893):1221–4.CrossRef Brody DL, Magnoni S, Schwetye KE, et al. Amyloid-β dynamics correlate with neurological status in the injured human brain. Science. 2008;321(5893):1221–4.CrossRef
48.
go back to reference Zsigmond P, Dernroth N, Kullman A, et al. Stereotactic microdialysis of the basal ganglia in Parkinson’s disease. J Neurosci Methods. 2012;207:17–22.CrossRef Zsigmond P, Dernroth N, Kullman A, et al. Stereotactic microdialysis of the basal ganglia in Parkinson’s disease. J Neurosci Methods. 2012;207:17–22.CrossRef
49.
go back to reference Feichtner F, Schaller R, Fercher A, et al. Microdialysis based device for continuous extravascular monitoring of blood glucose. Biomed Microdevices. 2010;12:399–407.CrossRef Feichtner F, Schaller R, Fercher A, et al. Microdialysis based device for continuous extravascular monitoring of blood glucose. Biomed Microdevices. 2010;12:399–407.CrossRef
50.
go back to reference Rooyackers O, Blixt C, Mattsson P, Wernerman J. Continuous glucose monitoring by intravenous microdialysis. Acta Anaesthesiol Scand. 2010;54(7):841–7.CrossRef Rooyackers O, Blixt C, Mattsson P, Wernerman J. Continuous glucose monitoring by intravenous microdialysis. Acta Anaesthesiol Scand. 2010;54(7):841–7.CrossRef
51.
go back to reference Helmark IC, Mikkelsen UR, Børglum J, et al. Exercise increases interleukin-10 levels in both intraarticularly and peri-synovially in patients with knee osteoarthritis: a randomized controlled trial. Arth Res Ther. 2010;12:R126–37.CrossRef Helmark IC, Mikkelsen UR, Børglum J, et al. Exercise increases interleukin-10 levels in both intraarticularly and peri-synovially in patients with knee osteoarthritis: a randomized controlled trial. Arth Res Ther. 2010;12:R126–37.CrossRef
Metadata
Title
Role of Microdialysis in Pharmacokinetics and Pharmacodynamics: Current Status and Future Directions
Authors
Francine Johansson Azeredo
Teresa Dalla Costa
Hartmut Derendorf
Publication date
01-03-2014
Publisher
Springer International Publishing
Published in
Clinical Pharmacokinetics / Issue 3/2014
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI
https://doi.org/10.1007/s40262-014-0131-8

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