The AAPS Journal

, Volume 19, Issue 2, pp 334–342 | Cite as

Utility of Microdialysis in Infectious Disease Drug Development and Dose Optimization

  • Amelia N. Deitchman
  • M. Tobias Heinrichs
  • Vipada Khaowroongrueng
  • Satyawan B. Jadhav
  • Hartmut Derendorf
Review Article Theme: Integrating Microdialysis and Imaging Tools in Systems Pharmacology
Part of the following topical collections:
  1. Theme: Integrating Microdialysis and Imaging Tools in Systems Pharmacology


Adequate drug penetration to a site of infection is absolutely imperative to ensure sufficient antimicrobial treatment. Microdialysis is a minimally invasive, versatile technique, which can be used to study the penetration of an antiinfective agent in virtually any tissue of interest. It has been used to investigate drug distribution and pharmacokinetics in variable patient populations, as a tool in dose optimization, a potential utility in therapeutic drug management, and in the study of biomarkers of disease progression. While all of these applications have not been fully explored in the field of antiinfectives, this review provides an overview of how microdialysis has been applied in various phases of drug development, a focus on the specific applications in the subspecialties of infectious disease (treatment of bacterial, fungal, viral, parasitic, and mycobacterial infections), and developing applications (biomarkers and therapeutic drug management).


antibiotics antivirals drug penetration pharmacodynamics pharmacokinetics 



A.N.D. would like to thank the American Foundation for Pharmaceutical Education for their support through the Pre-Doctoral Fellowship in Pharmaceutical Sciences.


  1. 1.
    Chaurasia CS, Müller M, Bashaw ED, Benfeldt E, Bolinder J, Bullock R, et al. AAPS-FDA workshop white paper: microdialysis principles, application and regulatory perspectives. Pharm Res. 2007;24(5):1014–25.PubMedCrossRefGoogle Scholar
  2. 2.
    Mindermann T, Zimmerli W, Gratzl O. Rifampin concentrations in various compartments of the human brain: a novel method for determining drug levels in the cerebral extracellular space. Antimicrob Agents Chemother. 1998;42(10):2626–9.PubMedPubMedCentralGoogle Scholar
  3. 3.
    Kempker RR, Barth AB, Vashakidze S, Nikolaishvili K, Sabulua I, Tukvadze N, et al. Cavitary penetration of levofloxacin among patients with multidrug-resistant tuberculosis. Antimicrob Agents Chemother. 2015;59(6):3149–55.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Traunmüller F, Schintler MV, Spendel S, Popovic M, Mauric O, Scharnagl E, et al. Linezolid concentrations in infected soft tissue and bone following repetitive doses in diabetic patients with bacterial foot infections. Int J Antimicrob Agents. 2010;36(1):84–6.PubMedCrossRefGoogle Scholar
  5. 5.
    Burkhardt O, Brunner M, Schmidt S, Grant M, Tang Y, Derendorf H. Penetration of ertapenem into skeletal muscle and subcutaneous adipose tissue in healthy volunteers measured by in vivo microdialysis. J Antimicrob Chemother. 2006;58(3):632–6.PubMedCrossRefGoogle Scholar
  6. 6.
    Müller M. Monitoring tissue drug levels by clinical microdialysis. Altern Lab Anim. 2009;37 Suppl 1:57–9.PubMedGoogle Scholar
  7. 7.
    Schmidt S, Banks R, Kumar V, Rand KH, Derendorf H. Clinical microdialysis in skin and soft tissues: an update. J Clin Pharmacol. 2008;48(3):351–64.PubMedCrossRefGoogle Scholar
  8. 8.
    Schroepf S, Burau D, Muench H-G, Derendorf H, Adam D, Kloft C. Microdialysis for therapeutic drug monitoring in infants. In: Poster abstract presented at: 8th International Symposium on Microdialysis. Uppsala, Sweden; 2016.Google Scholar
  9. 9.
    Deitchman AN, Derendorf H. Measuring drug distribution in the critically ill patient. Adv Drug Deliv Rev. 2014;77.Google Scholar
  10. 10.
    Plock N, Kloft C. Microdialysis—theoretical background and recent implementation in applied life-sciences. Eur J Pharm Sci. 2005;25(1):1–24.PubMedCrossRefGoogle Scholar
  11. 11.
    MacVane SH, Housman ST, Nicolau DP. In vitro microdialysis membrane efficiency of broad-spectrum antibiotics in combination and alone. Clin Pharmacol. 2014;6:97–101.PubMedPubMedCentralGoogle Scholar
  12. 12.
    Mukker JK, Singh RP, Derendorf H. Determination of atypical nonlinear plasma–protein-binding behavior of tigecycline using an in vitro microdialysis technique. J Pharm Sci. 2014;103(3):1013–9.PubMedCrossRefGoogle Scholar
  13. 13.
    US Food and Drug Administration. Guidance for Industry: Antiviral Product Development—Conducting and Submitting Virology Studies to the Agency. 2006.Google Scholar
  14. 14.
    US Food and Drug Administration. Guidance for Industry: Microbiology Data for Systemic Antibacterial Drugs—Development, Analysis, and Presentation. 2016.Google Scholar
  15. 15.
    Schmidt S, Röck K, Sahre M, Burkhardt O, Brunner M, Lobmeyer MT, et al. Effect of protein binding on the pharmacological activity of highly bound antibiotics. Antimicrob Agents Chemother. 2008;52(11):3994–4000.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    De La Peña A, Liu P, Derendorf H. Microdialysis in peripheral tissues. Adv Drug Deliv Rev. 2000:189–216.Google Scholar
  17. 17.
    Dhanani J, Roberts JA, Chew M, Lipman J, Boots RJ, Paterson DL, et al. Antimicrobial chemotherapy and lung microdialysis: a review. Int J Antimicrob Agents. 2010;36(6):491–500.PubMedCrossRefGoogle Scholar
  18. 18.
    Notkina N, Dahyot-Fizelier C, Gupta AK. In vivo microdialysis in pharmacological studies of antibacterial agents in the brain. Br J Anaesth. 2012;109(2):155–60.PubMedCrossRefGoogle Scholar
  19. 19.
    Bue M, Birke-Sørensen H, Thillemann TM, Hardlei TF, Søballe K, Tøttrup M. Single-dose pharmacokinetics of vancomycin in porcine cancellous and cortical bone determined by microdialysis. Int J Antimicrob Agents. 2015;46(4):434–8.PubMedCrossRefGoogle Scholar
  20. 20.
    Hurtado KF, Laureano JV, de A Lock G, Derendorf H, Dalla Costa T. Enhanced penetration of moxifloxacin into rat prostate tissue evidenced by microdialysis. Int J Antimicrob Agents. 2014;44(4):327–33.CrossRefGoogle Scholar
  21. 21.
    Cheung BWY, Liu W, Ji P, Cartier LL, Li Z, Mostafa N, et al. The chinchilla microdialysis model for the study of antibiotic distribution to middle ear fluid. AAPS J. 2006;8(1):E41–7.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    de Araújo BV, Laureano JV, Grünspan LD, Dalla Costa T, Tasso L. Validation of an efficient LC-microdialysis method for gemifloxacin quantitation in lung, kidney and liver of rats. J Chromatogr B Analyt Technol Biomed Life Sci. 2013;919–920:62–6.PubMedCrossRefGoogle Scholar
  23. 23.
    Macha S, Mitra AK. Ocular pharmacokinetics of cephalosporins using microdialysis. J Ocul Pharmacol Ther. 2001;17(5):485–98.PubMedCrossRefGoogle Scholar
  24. 24.
    Chang Y-L, Chiou S-H, Chou Y-C, Yen C-J, Tsai T-H. Quantitative determination of unbound cefoperazone in rat bile using microdialysis and liquid chromatography. J Pharm Biomed Anal. 2007;45(1):158–63.PubMedCrossRefGoogle Scholar
  25. 25.
    Sammeta SM, Vaka SRK, Murthy SN. Dermal drug levels of antibiotic (cephalexin) determined by electroporation and transcutaneous sampling (ETS) technique. J Pharm Sci. 2009;98(8):2677–85.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Tsai TH. Pharmacokinetics of pefloxacin and its interaction with cyclosporin A, a P-glycoprotein modulator, in rat blood, brain and bile, using simultaneous microdialysis. Br J Pharmacol. 2001;132(6):1310–6.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Hosoya K, Makihara A, Tsujikawa Y, Yoneyama D, Mori S, Terasaki T, et al. Roles of inner blood-retinal barrier organic anion transporter 3 in the vitreous/retina-to-blood efflux transport of p-aminohippuric acid, benzylpenicillin, and 6-mercaptopurine. J Pharmacol Exp Ther. 2009;329(1):87–93.PubMedCrossRefGoogle Scholar
  28. 28.
    Xin H-L, He X-R, Li W, Zhou Z-D, Zhang S, Wang G-J. The effect of borneol on the concentration of meropenem in rat brain and blood. J Asian Nat Prod Res. 2014;16(6):648–57.PubMedCrossRefGoogle Scholar
  29. 29.
    Gao W, Kishida T, Kageyama M, Kimura K, Yoshikawa Y, Shibata N, et al. Hepatic and intestinal contributions to pharmacokinetic interaction of indinavir with amprenavir, nelfinavir and saquinavir in rats. Antivir Chem Chemother. 2002;13(1):17–26.PubMedCrossRefGoogle Scholar
  30. 30.
    Waga J, Ehinger B. Intravitreal concentrations of some drugs administered with microdialysis. Acta Ophthalmol Scand. 1997;75(1):36–40.PubMedCrossRefGoogle Scholar
  31. 31.
    Liu P, Derendorf H. Antimicrobial tissue concentrations. Infect Dis Clin N Am. 2003;17(3):599–613.CrossRefGoogle Scholar
  32. 32.
    Joukhadar C, Derendorf H, Müller M. Microdialysis: a novel tool for clinical studies of anti-infective agents. Eur J Clin Pharmacol. 2001;57(3):211–9.PubMedCrossRefGoogle Scholar
  33. 33.
    Schwameis R, Zeitlinger M. Methods to measure target site penetration of antibiotics in critically ill patients. Curr Clin Pharmacol. 2013;8(1):46–58.PubMedGoogle Scholar
  34. 34.
    Shannon RJ, Carpenter KLH, Guilfoyle MR, Helmy A, Hutchinson PJ. Cerebral microdialysis in clinical studies of drugs: pharmacokinetic applications. J Pharmacokinet Pharmacodyn. 2013;40(3):343–58.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Traunmüller F, Schintler MV, Metzler J, Spendel S, Mauric O, Popovic M, et al. Soft tissue and bone penetration abilities of daptomycin in diabetic patients with bacterial foot infections. J Antimicrob Chemother. 2010;65(6):1252–7.PubMedCrossRefGoogle Scholar
  36. 36.
    Schintler MV, Traunmüller F, Metzler J, Kreuzwirt G, Spendel S, Mauric O, et al. High fosfomycin concentrations in bone and peripheral soft tissue in diabetic patients presenting with bacterial foot infection. J Antimicrob Chemother. 2009;64(3):574–8.PubMedCrossRefGoogle Scholar
  37. 37.
    Himebauch AS, Nicolson SC, Sisko M, Moorthy G, Fuller S, Gaynor JW, et al. Skeletal muscle and plasma concentrations of cefazolin during cardiac surgery in infants. J Thorac Cardiovasc Surg. 2014;148(6):2634–41.PubMedCrossRefGoogle Scholar
  38. 38.
    Langer O, Karch R, Müller U, Dobrozemsky G, Abrahim A, Zeitlinger M, et al. Combined PET and microdialysis for in vivo assessment of intracellular drug pharmacokinetics in humans. J Nucl Med. 2005;46(11):1835–41.PubMedGoogle Scholar
  39. 39.
    Liu P, Müller M, Derendorf H. Rational dosing of antibiotics: the use of plasma concentrations versus tissue concentrations. Int J Antimicrob Agents. 2002:285–90.Google Scholar
  40. 40.
    Schmidt S, Barbour A, Sahre M, Rand KH, Derendorf H. PK/PD: new insights for antibacterial and antiviral applications. Curr Opin Pharmacol. 2008;8(5):549–56.PubMedCrossRefGoogle Scholar
  41. 41.
    Brunner M, Derendorf H, Müller M. Microdialysis for in vivo pharmacokinetic/pharmacodynamic characterization of anti-infective drugs. Curr Opin Pharmacol. 2005:495–9.Google Scholar
  42. 42.
    Barbour AM, Schmidt S, Zhuang L, Rand K, Derendorf H. Application of pharmacokinetic/pharmacodynamic modelling and simulation for the prediction of target attainment of ceftobiprole against meticillin-resistant Staphylococcus aureus using minimum inhibitory concentration and time-kill curve based approaches. Int J Antimicrob Agents. Elsevier B.V.; 2014;43(1):60–7.Google Scholar
  43. 43.
    Bartek J, Thelin EP, Ghatan PH, Glimaker M, Bellander B-M. Neuron-specific enolase is correlated to compromised cerebral metabolism in patients suffering from acute bacterial meningitis. An observational cohort study. PLoS ONE. 2016;11(3), e0152268.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Radolf S, Smoll N, Drenckhahn C, Dreier JP, Vajkoczy P, Sarrafzadeh AS. Cerebral lactate correlates with early onset pneumonia after aneurysmal SAH. Transl Stroke Res. 2014;5(2):278–85.PubMedCrossRefGoogle Scholar
  45. 45.
    Schlenk F, Frieler K, Nagel A, Vajkoczy P, Sarrafzadeh AS. Cerebral microdialysis for detection of bacterial meningitis in aneurysmal subarachnoid hemorrhage patients: a cohort study. Crit Care. 2009;13(1):R2.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Poulsen FR, Schulz M, Jacobsen A, Andersen ÅB, Larsen L, Schalén W, et al. Bedside evaluation of cerebral energy metabolism in severe community-acquired bacterial meningitis. Neurocrit Care. 2015;22(2):221–8.PubMedCrossRefGoogle Scholar
  47. 47.
    Zeitlinger M, Müller M, Joukhadar C. Lung microdialysis—a powerful tool for the determination of exogenous and endogenous compounds in the lower respiratory tract (mini-review). AAPS J. 2005;7(3):E600–8.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Schuck EL, Grant M, Derendorf H. Effect of simulated microgravity on the disposition and tissue penetration of ciprofloxacin in healthy volunteers. J Clin Pharmacol. 2005;45(7):822–31.PubMedCrossRefGoogle Scholar
  49. 49.
    Dalley AJ, Lipman J, Deans R, Venkatesh B, Rudd M, Roberts MS, et al. Tissue accumulation of cephalothin in burns: a comparative study by microdialysis of subcutaneous interstitial fluid cephalothin concentrations in burn patients and healthy volunteers. Antimicrob Agents Chemother. 2009;53(1):210–5.PubMedCrossRefGoogle Scholar
  50. 50.
    Joukhadar C, Frossard M, Mayer BX, Brunner M, Klein N, Siostrzonek P, et al. Impaired target site penetration of beta-lactams may account for therapeutic failure in patients with septic shock. Crit Care Med. 2001;29(2):385–91.PubMedCrossRefGoogle Scholar
  51. 51.
    Roberts JA, Kirkpatrick CMJ, Roberts MS, Robertson TA, Dalley AJ, Lipman J. Meropenem dosing in critically ill patients with sepsis and without renal dysfunction: intermittent bolus versus continuous administration? Monte Carlo dosing simulations and subcutaneous tissue distribution. J Antimicrob Chemother. 2009;64(1):142–50.PubMedCrossRefGoogle Scholar
  52. 52.
    Brunner M, Stabeta H, Möller J-G, Schrolnberger C, Erovic B, Hollenstein U, et al. Target site concentrations of ciprofloxacin after single intravenous and oral doses. Antimicrob Agents Chemother. 2002;46(12):3724–30.PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    de la Pena A, Brunner M, Eichler H, Rehak E, Gross J, Thyroff-Friesinger U, et al. Comparative target site pharmacokinetics of immediate and modified-release formulations of cefaclor in humans. J Clin Pharmacol. 2002;42:403–11.CrossRefGoogle Scholar
  54. 54.
    Raney SG, Franz TJ, Lehman PA, Lionberger R, Chen M-L. Pharmacokinetics-based approaches for bioequivalence evaluation of topical dermatological drug products. Clin Pharmacokinet. 2015;54(11):1095–106.PubMedCrossRefGoogle Scholar
  55. 55.
    Incecayir T, Agabeyoglu I, Derici U, Sindel S. Assessment of topical bioequivalence using dermal microdialysis and tape stripping methods. Pharm Res. 2011;28(9):2165–75.PubMedCrossRefGoogle Scholar
  56. 56.
    Brill MJE, Houwink API, Schmidt S, Van Dongen EPA, Hazebroek EJ, van Ramshorst B, et al. Reduced subcutaneous tissue distribution of cefazolin in morbidly obese versus non-obese patients determined using clinical microdialysis. J Antimicrob Chemother. 2014;69(3):715–23.PubMedCrossRefGoogle Scholar
  57. 57.
    Barbour A, Schmidt S, Rout WR, Ben-David K, Burkhardt O, Derendorf H. Soft tissue penetration of cefuroxime determined by clinical microdialysis in morbidly obese patients undergoing abdominal surgery. Int J Antimicrob Agents. 2009;34(3):231–5.PubMedCrossRefGoogle Scholar
  58. 58.
    Varghese JM, Jarrett P, Wallis SC, Boots RJ, Kirkpatrick CMJ, Lipman J, et al. Are interstitial fluid concentrations of meropenem equivalent to plasma concentrations in critically ill patients receiving continuous renal replacement therapy? J Antimicrob Chemother. 2015;70(2):528–33.PubMedCrossRefGoogle Scholar
  59. 59.
    Ray A, Malin D, Nicolau DP, Wiskirchen DE. Antibiotic tissue penetration in diabetic foot infections a review of the microdialysis literature and needs for future research. J Am Podiatr Med Assoc. 2015;105(6):520–31.PubMedCrossRefGoogle Scholar
  60. 60.
    Boyadjiev I, Boulamery A, Simon N, Martin C, Bruguerolle B, Leone M. Penetration of ertapenem into muscle measured by in vivo microdialysis in mechanically ventilated patients. Antimicrob Agents Chemother. 2011;55(7):3573–5.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Karjagin J, Lefeuvre S, Oselin K, Kipper K, Marchand S, Tikkerberi A, et al. Pharmacokinetics of meropenem determined by microdialysis in the peritoneal fluid of patients with severe peritonitis associated with septic shock. Clin Pharmacol Ther. 2008;83(3):452–9.Google Scholar
  62. 62.
    Barbour A, Schmidt S, Sabarinath SN, Grant M, Seubert C, Skee D, et al. Soft-tissue penetration of ceftobiprole in healthy volunteers determined by in vivo microdialysis. Antimicrob Agents Chemother. 2009;53(7):2773–6.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Hollenstein U, Brunner M, Mayer BX, Delacher S, Erovic B, Eichler HG, et al. Target site concentrations after continuous infusion and bolus injection of cefpirome to healthy volunteers. Clin Pharmacol Ther. 2000;67(3):229–36.PubMedCrossRefGoogle Scholar
  64. 64.
    Enting RH, Hoetelmans RM, Lange JM, Burger DM, Beijnen JH, Portegies P. Antiretroviral drugs and the central nervous system. AIDS. 1998;12(15):1941–55.PubMedCrossRefGoogle Scholar
  65. 65.
    Boddu SHS, Gunda S, Earla R, Mitra AK. Ocular microdialysis: a continuous sampling technique to study pharmacokinetics and pharmacodynamics in the eye. Bioanalysis. 2010;2(3):487–507.PubMedCrossRefGoogle Scholar
  66. 66.
    Klimowicz A, Farfał S, Bielecka-Grzela S. Evaluation of skin penetration of topically applied drugs in humans by cutaneous microdialysis: acyclovir vs. salicylic acid. J Clin Pharm Ther. 2007;32(2):143–8.PubMedCrossRefGoogle Scholar
  67. 67.
    Morgan CJ, Renwick AG, Friedmann PS. The role of stratum corneum and dermal microvascular perfusion in penetration and tissue levels of water-soluble drugs investigated by microdialysis. Br J Dermatol. 2003;148(3):434–43.PubMedCrossRefGoogle Scholar
  68. 68.
    Borg N, Götharson E, Benfeldt E, Groth L, Ståhle L. Distribution to the skin of penciclovir after oral famciclovir administration in healthy volunteers: comparison of the suction blister technique and cutaneous microdialysis. Acta Derm Venereol. 1999;79(4):274–7.PubMedCrossRefGoogle Scholar
  69. 69.
    Farfal S, Klimowicz A, Bielecka-Grzela S. Acyclovir concentrations in the skin of humans after a single oral dose assessed by in vivo cutaneous microdialysis. Skin Res Technol. 2006;12(4):228–34.PubMedCrossRefGoogle Scholar
  70. 70.
    Simmel F, Kloft C. Microdialysis feasibility investigations with the non-hydrophilic antifungal voriconazole for potential applications in nonclinical and clinical settings. Int J Clin Pharmacol Ther. 2010;48(11):695–704.PubMedCrossRefGoogle Scholar
  71. 71.
    Tre ES, Patel C, Aghara S, Yadav C, Stagni G. Optimization of perfusate pH to improve microdialysis recovery of lipophilic compounds. J Pharmacol Toxicol Methods. 66(3):276–80.Google Scholar
  72. 72.
    Sinnollareddy MG, Roberts MS, Lipman J, Peake SL, Roberts JA. Influence of sustained low-efficiency diafiltration (SLED-f) on interstitial fluid concentrations of fluconazole in a critically ill patient: use of microdialysis. Int J Antimicrob Agents. 2015;46(1):121–4.PubMedCrossRefGoogle Scholar
  73. 73.
    Sinnollareddy MG, Roberts MS, Lipman J, Lassig-Smith M, Starr T, Robertson T, et al. In vivo microdialysis to determine subcutaneous interstitial fluid penetration and pharmacokinetics of fluconazole in intensive care unit patients with sepsis. Antimicrob Agents Chemother. 2016;60(2):827–32.PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Sasongko L, Williams KM, Day RO, McLachlan AJ. Human subcutaneous tissue distribution of fluconazole: comparison of microdialysis and suction blister techniques. Br J Clin Pharmacol. 2003;56(5):551–61.PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Simmel F, Kirbs C, Erdogan Z, Lackner E, Zeitlinger M, Kloft C. Pilot investigation on long-term subcutaneous microdialysis: proof of principle in humans. AAPS J. 2013;15(1):95–103.PubMedCrossRefGoogle Scholar
  76. 76.
    Sun N, Xie Y, Sheng C, Cao Y, Zhang W, Chen H, et al. In vivo pharmacokinetics and in vitro antifungal activity of iodiconazole, a new triazole, determined by microdialysis sampling. Int J Antimicrob Agents. 2013;41(3):229–35.PubMedCrossRefGoogle Scholar
  77. 77.
    Mathy F-X, Ntivunwa D, Verbeeck RK, Préat V. Fluconazole distribution in rat dermis following intravenous and topical application: a microdialysis study. J Pharm Sci. 2005;94(4):770–80.PubMedCrossRefGoogle Scholar
  78. 78.
    Azeredo FJ, de Araújo BV, Haas SE, Torres B, Pigatto M, de Andrade C, et al. Comparison of fluconazole renal penetration levels in healthy and Candida albicans-infected Wistar rats. Antimicrob Agents Chemother. 2012;56(11):5852–7.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    de Araujo BV, da Silva CF, Haas SE, Dalla Costa T. Free renal levels of voriconazole determined by microdialysis in healthy and Candida sp.-infected Wistar rats. Int J Antimicrob Agents. 2009;33(2):154–9.PubMedCrossRefGoogle Scholar
  80. 80.
    Yang H, Wang Q, Elmquist WF. Fluconazole distribution to the brain: a crossover study in freely-moving rats using in vivo microdialysis. Pharm Res. 1996;13(10):1570–5.PubMedCrossRefGoogle Scholar
  81. 81.
    Gratieri T, Gelfuso GM, de Freitas O, Rocha EM, Lopez RFV. Enhancing and sustaining the topical ocular delivery of fluconazole using chitosan solution and poloxamer/chitosan in situ forming gel. Eur J Pharm Biopharm Off J Arbeitsgemeinschaft für Pharm Verfahrenstechnik eV. 2011;79(2):320–7.Google Scholar
  82. 82.
    Mauric O, Thallinger C, Kugler SA, Joukhadar SM, Kovar FM, Konz KH, et al. The ability of fluconazole to penetrate into ventilated, healthy and inflamed lung tissue in a model of severe sepsis in rats. Pharmacology. 2011;87(3–4):130–4.PubMedCrossRefGoogle Scholar
  83. 83.
    Joukhadar C, Thallinger C, Pöppl W, Kovar F, Konz KH, Joukhadar SM, et al. Concentrations of voriconazole in healthy and inflamed lung in rats. Antimicrob Agents Chemother. 2009;53(6):2684–6.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Saunte DM, Simmel F, Frimodt-Moller N, Stolle LB, Svejgaard EL, Haedersdal M, et al. In vivo efficacy and pharmacokinetics of voriconazole in an animal model of dermatophytosis. Antimicrob Agents Chemother. 2007;51(9):3317–21.PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Kempker R, Heinrichs M, Vashakidze S, Nikolaishvili K, Sabulua I, Tukvadze N, et al. Lung tissue concentrations of pyrazinamide among patients with tuberculosis. In: 9th International Workshop on Clinical Pharmacology of Tuberculosis Drugs. Liverpool, United Kingdom; 2016.Google Scholar
  86. 86.
    Voelkner N, Voelkner A, Kima P, Derendorf H. Dose optimization of pyrazinamide based on dermal microdialysis in Wistar rats for cutaneous leishmaniasis treatment. In: Poster abstract presented at: 8th International Symposium on Microdialysis. Uppsala, Sweden; 2016.Google Scholar
  87. 87.
    David CN, Frias ES, Szu JI, Vieira PA, Hubbard JA, Lovelace J, et al. GLT-1-dependent disruption of CNS glutamate homeostasis and neuronal function by the protozoan parasite Toxoplasma gondii. PLoS Pathog. 2016;12(6):e1005643.PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Brazís P, Barandica L, García F, Clough GF, Church MK, Puigdemont A. Dermal microdialysis in the dog: in vivo assessment of the effect of cyclosporin A on cutaneous histamine and prostaglandin D2 release. Vet Dermatol. 2006;17(3):169–74.PubMedCrossRefGoogle Scholar
  89. 89.
    Romarís F, Iglesias R, García LO, Leiro J, Santamarina MT, Paniagua E, et al. Free and bound biotin molecules in helminths: a source of artifacts for avidin biotin-based immunoassays. Parasitol Res. 1996;82(7):617–22.PubMedCrossRefGoogle Scholar
  90. 90.
    Caljon G, Caveliers V, Lahoutte T, Stijlemans B, Ghassabeh GH, Van Den Abbeele J, et al. Using microdialysis to analyse the passage of monovalent nanobodies through the blood–brain barrier. Br J Pharmacol. 2012;165(7):2341–53.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Jadhav S, Khaowroongrueng V, Derendorf H. Microdialysis of large molecules. J Pharm Sci, Accept Manuscr. 2016.Google Scholar
  92. 92.
    Kirbs C. Development and application of an in vitro and in vivo microdialysis methods contributing to biomarker profiling and characterisation of drug distribution processes. 2015.Google Scholar
  93. 93.
    Dragatin C, Polus F, Bodenlenz M, Calonder C, Aigner B, Tiffner KI, et al. Secukinumab distributes into dermal interstitial fluid of psoriasis patients as demonstrated by open flow microperfusion. Exp Dermatol. 2016;25(2):157–9.PubMedCrossRefGoogle Scholar
  94. 94.
    Jadhav SB, Khaowroongrueng V, Fueth M, Richter W, Ottender M, Derendorf H. In vitro microdialysis of a monoclonal antibody. In: Abstract presented at 8th International Symposium on Microdialysis. Uppsala, Sweden; 2016.Google Scholar
  95. 95.
    Morrison C. Antibacterial antibodies gain traction. Nat Rev Drug Discov. 2015;14(11):737–8.PubMedCrossRefGoogle Scholar
  96. 96.
    Herkner H, Müller MRM, Kreischitz N, Mayer BX, Frossard M, Joukhadar C, et al. Closed-chest microdialysis to measure antibiotic penetration into human lung tissue. Am J Respir Crit Care Med. 2002;165(2):273–6.PubMedCrossRefGoogle Scholar
  97. 97.
    Roberts JA, Abdul-Aziz MH, Lipman J, Mouton JW, Vinks AA, Felton TW, et al. Individualised antibiotic dosing for patients who are critically ill: challenges and potential solutions. Lancet Infect Dis. 2014;14(6):498–509.PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Wicha SG, Kees MG, Solms A, Minichmayr IK, Kratzer A, Kloft C. TDMx: a novel web-based open-access support tool for optimising antimicrobial dosing regimens in clinical routine. Int J Antimicrob Agents. 2015;45(4):442–4.PubMedCrossRefGoogle Scholar
  99. 99.
    Schaeftlein A, Minichmayr IK, Kloft C. Population pharmacokinetics meets microdialysis: benefits, pitfalls and necessities of new analysis approaches for human microdialysis data. Eur J Pharm Sci. 2014;57:68–73.PubMedCrossRefGoogle Scholar
  100. 100.
    US Food and Drug Administration. In Vitro Companion Diagnostic Devices: Guidance for Industry and Food and Drug Administration Staff. 2014.Google Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2016

Authors and Affiliations

  • Amelia N. Deitchman
    • 1
  • M. Tobias Heinrichs
    • 1
  • Vipada Khaowroongrueng
    • 1
  • Satyawan B. Jadhav
    • 1
  • Hartmut Derendorf
    • 1
  1. 1.Department of PharmaceuticsUniversity of FloridaGainesvilleUSA

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