Microdialysis in Antibiotic Research

  • Markus Zeitlinger
  • Sandrine Marchand
  • William Couet
  • Aline Barth
  • Hartmut Derendorf
Chapter
Part of the AAPS Advances in the Pharmaceutical Sciences Series book series (AAPS, volume 4)

Abstract

Traditionally, the PK of different anti-infective drugs is evaluated based on the plasma drug concentrations. However, in some cases those concentrations are not identical to those detected at the target site of the infection, i.e., in the affected tissue. In this context, microdialysis is a valuable technique applied for the quantification of free drug in the interstitial space fluid of a great variety of tissues. Considering that generally the infections are located in interstitial space fluid and only the free drug fraction is able to exert the anti-infective effect, it is clear that this approach has the necessary features to quantify the active fraction at the site of action. Using this information for consecutive pharmacokinetic/pharmacodynamic models is increasingly becoming state-of-the-art for optimizing dosing regimens of antibiotics.

Keywords

High Performance Liquid Chromatography Pneumonia Tuberculosis Morphine Radionuclide 

References

  1. Adembri C, Novelli A (2009) Pharmacokinetic and pharmacodynamic parameters of antimicrobials: potential for providing dosing regimens that are less vulnerable to resistance. Clin Pharmacokinet 48(8):517–528PubMedGoogle Scholar
  2. Alffenaar JW, van Altena R, Bokkerink HJ, Luijckx GJ, van Soolingen D, Aarnoutse RE, van der Werf TS (2009) Pharmacokinetics of moxifloxacin in cerebrospinal fluid and plasma in patients with tuberculous meningitis. Clin Infect Dis 49(7):1080–1082PubMedGoogle Scholar
  3. Andes D, Anon J, Jacobs MR, Craig WA (2004) Application of pharmacokinetics and pharmacodynamics to antimicrobial therapy of respiratory tract infections. Clin Lab Med 24(2):477–502PubMedGoogle Scholar
  4. Baldwin DR, Maxwell SR, Honeybourne D, Andrews JM, Ashby JP, Wise R (1991) The penetration of cefpirome into the potential sites of pulmonary infection. J Antimicrob Chemother 28(1):79–86PubMedGoogle Scholar
  5. Barbour A, Schmidt S, Rout WR, Ben-David K, Burkhardt O, Derendorf H (2009) Soft tissue penetration of cefuroxime determined by clinical microdialysis in morbidly obese patients undergoing abdominal surgery. Int J Antimicrob Agents 34(3):231–235PubMedGoogle Scholar
  6. Bebear CM, de Barbeyrac B, Pereyre S, Renaudin H, Clerc M, Bebear C (2008) Activity of moxifloxacin against the urogenital mycoplasmas Ureaplasma spp., Mycoplasma hominis and Mycoplasma genitalium and Chlamydia trachomatis. Clin Microbiol Infect 14(8):801–805PubMedGoogle Scholar
  7. Betancourt L, Rada P, Paredes D, Hernandez L (2012) In vivo monitoring of cerebral agmatine by microdialysis and capillary electrophoresis. J Chromatogr B Analyt Technol Biomed Life Sci 880(1):58–65PubMedGoogle Scholar
  8. Blondeau JM, Laskowski R, Bjarnason J, Stewart C (2000) Comparative in vitro activity of gatifloxacin, grepafloxacin, levofloxacin, moxifloxacin and trovafloxacin against 4151 Gram-negative and Gram-positive organisms. Int J Antimicrob Agents 14(1):45–50PubMedGoogle Scholar
  9. Brunner M, Derendorf H (2006) Clinical microdialysis: Current applications and potential use in drug development. Trends Anal Chem 25(7):674–680Google Scholar
  10. Brunner M, Langer O (2006) Microdialysis versus other techniques for the clinical assessment of in vivo tissue drug distribution. AAPS J 8(2): E263–E271Google Scholar
  11. Brunner M, Schmiedberger A, Schmid R, Jager D, Piegler E, Eichler HG, Muller M (1998) Direct assessment of peripheral pharmacokinetics in humans: comparison between cantharides blister fluid sampling, in vivo microdialysis and saliva sampling. Br J Clin Pharmacol 46(5):425–431PubMedGoogle Scholar
  12. Brunner M, Pernerstorfer T, Mayer BX, Eichler HG, Muller M (2000) Surgery and intensive care procedures affect the target site distribution of piperacillin. Crit Care Med 28(6):1754–1759PubMedGoogle Scholar
  13. Brunner M, Langer O, Dobrozemsky G, Muller U, Zeitlinger M, Mitterhauser M, Wadsak W, Dudczak R, Kletter K, Muller M (2004) [18F]Ciprofloxacin, a new positron emission tomography tracer for noninvasive assessment of the tissue distribution and pharmacokinetics of ciprofloxacin in humans. Antimicrob Agents Chemother 48(10):3850–3857PubMedGoogle Scholar
  14. Brunner M, Derendorf H, Muller M (2005) Microdialysis for in vivo pharmacokinetic/pharmacodynamic characterization of anti-infective drugs. Curr Opin Pharmacol 5(5):495–499PubMedGoogle Scholar
  15. Bulik CC, Wiskirchen DE, Shepard A, Sutherland CA, Kuti JL, Nicolau DP (2010) Tissue penetration and pharmacokinetics of tigecycline in diabetic patients with chronic wound infections described by using in vivo microdialysis. Antimicrob Agents Chemother 54(12):5209–5213PubMedGoogle Scholar
  16. Burkhardt O, Majcher-Peszynska J, Borner K, Mundkowski R, Drewelow B, Derendorf H, Welte T (2005) Penetration of ertapenem into different pulmonary compartments of patients undergoing lung surgery. J Clin Pharmacol 45(6):659–665PubMedGoogle Scholar
  17. Burkhardt O, Brunner M, Schmidt S, Grant M, Tang Y, Derendorf H (2006) Penetration of ertapenem into skeletal muscle and subcutaneous adipose tissue in healthy volunteers measured by in vivo microdialysis. J Antimicrob Chemother 58(3):632–636PubMedGoogle Scholar
  18. Capitano B, Mattoes HM, Shore E, O’Brien A, Braman S, Sutherland C, Nicolau DP (2004) Steady-state intrapulmonary concentrations of moxifloxacin, levofloxacin, and azithromycin in older adults. Chest 125(3):965–973PubMedGoogle Scholar
  19. Elmeliegy MA, Carcaboso AM, LM LC, Zhang ZM, Calabrese C, Throm SL, Wang F, Baker SJ, Stewart CF (2011) Magnetic resonance imaging-guided microdialysis cannula implantation in a spontaneous high-grade glioma murine model. J Pharm SciGoogle Scholar
  20. Chaurasia CS (1999) In vivo microdialysis sampling: theory and applications. Biomed Chromatogr 13(5):317–332PubMedGoogle Scholar
  21. Chu Y, Wang X, Guo J, Li W, Ma X, Zhu Y (2012) Pharmacokinetic study of unbound forsythiaside in rat blood and bile by microdialysis coupled with HPLC method. Eur J Drug Metab Pharmacokinet. Feb 7. [Epub ahead of print]Google Scholar
  22. Congeni BL (2010) Ertapenem. Expert Opin Pharmacother 11(4):669–672PubMedGoogle Scholar
  23. Cooley JC, Lunte CE (2011) Detection of malondialdehyde in vivo using microdialysis sampling with CE-fluorescence. Electrophoresis 32(21):2994–2999PubMedGoogle Scholar
  24. Craig WA, Suh B (1978) Changes in protein binding during disease. Scand J Infect Dis Suppl(14): 239–244Google Scholar
  25. Dahyot C, Marchand S, Bodin M, Debeane B, Mimoz O, Couet W (2008) Application of basic pharmacokinetic concepts to analysis of microdialysis data: illustration with imipenem muscle distribution. Clin Pharmacokinet 47(3):181–189PubMedGoogle Scholar
  26. Effros RM, Mason GR, Silverman P, Reid E, Hukkanen J (1986) Movement of ions and small solutes across endothelium and epithelium of perfused rabbit lungs. J Appl Physiol 60(1):100–107PubMedGoogle Scholar
  27. EMEA (2000) Points to consider on pharmacokinetics and pharmacodynamics in the development of antibacterial medicinal products. (www.emea.eu.int/pdfs/human/ewp/265599en.pdf)
  28. Evrard PA, Deridder G, Verbeeck RK (1996) Intravenous microdialysis in the mouse and the rat: development and pharmacokinetic application of a new probe. Pharm Res 13(1):12–17PubMedGoogle Scholar
  29. FDA (1998) Guidance for Industry. Developing antimicrobial drugs—general considerations for clinical trials. (www.fda.gov/cder/guidance/2580dft.pdf)
  30. Fischman AJ, Alpert NM, Babich JW, Rubin RH (1997) The role of positron emission tomography in pharmacokinetic analysis. Drug Metab Rev 29(4):923–956PubMedGoogle Scholar
  31. Fischman AJ, Babich JW, Bonab AA, Alpert NM, Vincent J, Callahan RJ, Correia JA, Rubin RH (1998) Pharmacokinetics of [18F]trovafloxacin in healthy human subjects studied with positron emission tomography. Antimicrob Agents Chemother 42(8):2048–2054PubMedGoogle Scholar
  32. Florea NR, Tessier PR, Zhang C, Nightingale CH, Nicolau DP (2004) Pharmacodynamics of moxifloxacin and levofloxacin at simulated epithelial lining fluid drug concentrations against Streptococcus pneumoniae. Antimicrob Agents Chemother 48(4):1215–1221PubMedGoogle Scholar
  33. Frossard M, Joukhadar C, Erovic BM, Dittrich P, Mrass PE, Van Houte M, Burgmann H, Georgopoulos A, Muller M (2000) Distribution and antimicrobial activity of fosfomycin in the interstitial fluid of human soft tissues. Antimicrob Agents Chemother 44(10):2728–2732PubMedGoogle Scholar
  34. Gonzalez D, Conrado DJ, Theuretzbacher U, Derendorf H (2011) The effect of critical illness on drug distribution. Curr Pharm Biotechnol 12(12):2030–2036PubMedGoogle Scholar
  35. Gotfried MH, Danziger LH, Rodvold KA (2001) Steady-state plasma and intrapulmonary concentrations of levofloxacin and ciprofloxacin in healthy adult subjects. Chest 119(4):1114–1122PubMedGoogle Scholar
  36. Hancock RE, Bellido F (1992) Factors involved in the enhanced efficacy against gram-negative bacteria of fourth generation cephalosporins. J Antimicrob Chemother 29(Suppl A): 1–6Google Scholar
  37. Hashiguti H, Nakahara D, Maruyama W, Naoi M, Ikeda T (1993) Simultaneous determination of in vivo hydroxylation of tyrosine and tryptophan in rat striatum by microdialysis-HPLC: relationship between dopamine and serotonin biosynthesis. J Neural Transm Gen Sect 93(3):213–223PubMedGoogle Scholar
  38. Hatfield T, Spanis C, McGaugh JL (1999) Response of amygdalar norepinephrine to footshock and GABAergic drugs using in vivo microdialysis and HPLC. Brain Res 835(2):340–345PubMedGoogle Scholar
  39. Herrera AM, Scott DO, Lunte CE (1990) Microdialysis sampling for determination of plasma protein binding of drugs. Pharm Res 7(10):1077–1081PubMedGoogle Scholar
  40. Hollenstein U, Brunner M, Mayer BX, Delacher S, Erovic B, Eichler HG, Muller M (2000) Target site concentrations after continuous infusion and bolus injection of cefpirome to healthy volunteers. Clin Pharmacol Ther 67(3):229–236PubMedGoogle Scholar
  41. Hollenstein UM, Brunner M, Schmid R, Muller M (2001) Soft tissue concentrations of ciprofloxacin in obese and lean subjects following weight-adjusted dosing. Int J Obes Relat Metab Disord 25(3):354–358PubMedGoogle Scholar
  42. Huang Y, Ji P, Inano A, Yang Z, Giebink GS, Sawchuk RJ (2001) Microdialysis studies of the middle ear distribution kinetics of amoxicillin in the awake chinchilla. J Pharm Sci 90(12):2088–2098PubMedGoogle Scholar
  43. Ikawa K, Morikawa N, Ikeda K, Ohge H, Sueda T (2008) Development of breakpoints of carbapenems for intraabdominal infections based on pharmacokinetics and pharmacodynamics in peritoneal fluid. J Infect Chemother 14(4):330–332PubMedGoogle Scholar
  44. Joukhadar C, Frossard M, Mayer BX, Brunner M, Klein N, Siostrzonek P, Eichler HG, Muller M (2001) Impaired target site penetration of beta-lactams may account for therapeutic failure in patients with septic shock. Crit Care Med 29(2):385–391PubMedGoogle Scholar
  45. Joukhadar C, Klein N, Mayer BX, Kreischitz N, Delle-Karth G, Palkovits P, Heinz G, Muller M (2002) Plasma and tissue pharmacokinetics of cefpirome in patients with sepsis. Crit Care Med 30(7):1478–1482PubMedGoogle Scholar
  46. Joukhadar C, Klein N, Dittrich P, Zeitlinger M, Geppert A, Skhirtladze K, Frossard M, Heinz G, Muller M (2003a) Target site penetration of fosfomycin in critically ill patients. J Antimicrob Chemother 51(5):1247–1252PubMedGoogle Scholar
  47. Joukhadar C, Stass H, Muller-Zellenberg U, Lackner E, Kovar F, Minar E, Muller M (2003b) Penetration of Moxifloxacin into Healthy and Inflamed Subcutaneous Adipose Tissues in Humans. Antimicrob Agents Chemother 47(10):3099–3103PubMedGoogle Scholar
  48. Kaul S, Faiman MD, Lunte CE (2011) Determination of GABA, glutamate and carbamathione in brain microdialysis samples by capillary electrophoresis with fluorescence detection. Electrophoresis 32(2):284–291PubMedGoogle Scholar
  49. Kavi J, Andrews JM, Ashby JP, Hillman G, Wise R (1988) Pharmacokinetics and tissue penetration of cefpirome, a new cephalosporin. J Antimicrob Chemother 22(6):911–916PubMedGoogle Scholar
  50. Kearney BP, Aweeka FT (1999) The penetration of anti-infectives into the central nervous system. Neurol Clin 17(4):883–900PubMedGoogle Scholar
  51. Keating GM, Scott LJ (2004) Moxifloxacin: a review of its use in the management of bacterial infections. Drugs 64(20):2347–2377PubMedGoogle Scholar
  52. Kikuchi J, Yamazaki K, Kikuchi E, Ishizaka A, Nishimura M (2007) Pharmacokinetics of gatifloxacin after a single oral dose in healthy young adult subjects and adult patients with chronic bronchitis, with a comparison of drug concentrations obtained by bronchoscopic microsampling and bronchoalveolar lavage. Clin Ther 29(1):123–130PubMedGoogle Scholar
  53. Kikuchi E, Yamazaki K, Kikuchi J, Hasegawa N, Hashimoto S, Ishizaka A, Nishimura M (2008) Pharmacokinetics of clarithromycin in bronchial epithelial lining fluid. Respirology 13(2):221–226PubMedGoogle Scholar
  54. Kim A, Suecof LA, Sutherland CA, Gao L, Kuti JL, Nicolau DP (2008) In vivo microdialysis study of the penetration of daptomycin into soft tissues in diabetic versus healthy volunteers. Antimicrob Agents Chemother 52(11):3941–3946PubMedGoogle Scholar
  55. Kinzig M, Sorgel F, Brismar B, Nord CE (1992) Pharmacokinetics and tissue penetration of tazobactam and piperacillin in patients undergoing colorectal surgery. Antimicrob Agents Chemother 36(9):1997–2004PubMedGoogle Scholar
  56. Korting HC, Schafer-Korting M, Maass L, Klesel N, Mutschler E (1987) Cefodizime in serum and skin blister fluid after single intravenous and intramuscular doses in healthy volunteers. Antimicrob Agents Chemother 31(11):1822–1825PubMedGoogle Scholar
  57. Kovar A, Dalla Costa T, Derendorf H (1997) Comparison of plasma and free tissue levels of ceftriaxone in rats by microdialysis. J Pharm Sci 86(1):52–56PubMedGoogle Scholar
  58. Kullar R, Chin JN, Edwards DJ, Parker D, Coplin WM, Rybak MJ (2011) Pharmacokinetics of single-dose daptomycin in patients with suspected or confirmed neurological infections. Antimicrob Agents Chemother 55(7):3505–3509PubMedGoogle Scholar
  59. Laethem T, De Lepeleire I, McCrea J, Zhang J, Majumdar A, Musson D, Rogers D, Li S, Guillaume M, Parneix-Spake A, Deutsch P (2003) Tissue penetration by ertapenem, a parenteral carbapenem administered once daily, in suction-induced skin blister fluid in healthy young volunteers. Antimicrob Agents Chemother 47(4):1439–1442PubMedGoogle Scholar
  60. Langer O, Muller M (2004) Methods to assess tissue-specific distribution and metabolism of drugs. Curr Drug Metab 5(6):463–481PubMedGoogle Scholar
  61. Li Y, Peris J, Zhong L, Derendorf H (2006a) Microdialysis as a tool in local pharmacodynamics. AAPS J 8(2): E222–E235Google Scholar
  62. Li Y, Peris J, Zhong L, Derendorf H (2006b) Microdialysis as a tool in local pharmacodynamics. AAPS J 08(02):1–33Google Scholar
  63. Lipman J, Wallis SC, Rickard CM, Fraenkel D (2001) Low cefpirome levels during twice daily dosing in critically ill septic patients: pharmacokinetic modelling calls for more frequent dosing. Intensive Care Med 27(2):363–370PubMedGoogle Scholar
  64. Liu P, Fuhrherr R, Webb AI, Obermann B, Derendorf H (2005) Tissue penetration of cefpodoxime into the skeletal muscle and lung in rats. Eur J Pharm Sci 25(4–5):439–444PubMedGoogle Scholar
  65. Maggiolo F, Capra R, Bottura P, Pravettoni G, Migliorino M, Suter F (2000) In vitro activity of moxifloxacin combined with other antibacterials against methicillin-resistant Staphylococcus aureus. J Chemother 12(3):195–198PubMedGoogle Scholar
  66. Marchand S, Chenel M, Lamarche I, Couet W (2005a) Pharmacokinetic modeling of free amoxicillin concentrations in rat muscle extracellular fluids determined by microdialysis. Antimicrob Agents Chemother 49(9):3702–3706PubMedGoogle Scholar
  67. Marchand S, Dahyot C, Lamarche I, Mimoz O, Couet W (2005b) Microdialysis study of imipenem distribution in skeletal muscle and lung extracellular fluids of noninfected rats. Antimicrob Agents Chemother 49(6):2356–2361PubMedGoogle Scholar
  68. Marchand S, Dahyot C, Lamarche I, Plan E, Mimoz O, Couet W (2005c) Lack of effect of experimental hypovolemia on imipenem muscle distribution in rats assessed by microdialysis. Antimicrob Agents Chemother 49(12):4974–4979PubMedGoogle Scholar
  69. Muller M, Haag O, Burgdorff T, Georgopoulos A, Weninger W, Jansen B, Stanek G, Pehamberger H, Agneter E, Eichler HG (1996) Characterization of peripheral-compartment kinetics of antibiotics by in vivo microdialysis in humans. Antimicrob Agents Chemother 40(12):2703–2709PubMedGoogle Scholar
  70. Muller M, Brunner M, Hollenstein U, Joukhadar C, Schmid R, Minar E, Ehringer H, Eichler HG (1999a) Penetration of ciprofloxacin into the interstitial space of inflamed foot lesions in non-insulin-dependent diabetes mellitus patients. Antimicrob Agents Chemother 43(8):2056–2058PubMedGoogle Scholar
  71. Muller M, Stass H, Brunner M, Moller JG, Lackner E, Eichler HG (1999b) Penetration of moxifloxacin into peripheral compartments in humans. Antimicrob Agents Chemother 43(10):2345–2349PubMedGoogle Scholar
  72. Muller M, dela Pena A, Derendorf H (2004). Issues in pharmacokinetics and pharmacodynamics of anti-infective agents: distribution in tissue. Antimicrob Agents Chemother 48(5): 1441–1453Google Scholar
  73. Nix DE, Wilton JH, Velasquez N, Budny JL, Lassman HB, Mitchell P, Divan K, Schentag JJ (1992) Cerebrospinal fluid penetration of cefpirome in patients with non-inflamed meninges. J Antimicrob Chemother 29(Suppl A): 51–57Google Scholar
  74. Nix DE, Matthias KR, Ferguson EC (2004) Effect of ertapenem protein binding on killing of bacteria. Antimicrob Agents Chemother 48(9):3419–3424PubMedGoogle Scholar
  75. Ober MC, Hoppe-Tichy T, Koninger J, Schunter O, Sonntag HG, Weigand MA, Encke J, Gutt C, Swoboda S (2009) Tissue penetration of moxifloxacin into human gallbladder wall in patients with biliary tract infections. J Antimicrob Chemother 64(5):1091–1095PubMedGoogle Scholar
  76. Perez-Trallero E, Garcia-Rey C, Martin-Sanchez AM, Aguilar L, Garcia-de-Lomas J, Ruiz J (2002) Activities of six different quinolones against clinical respiratory isolates of Streptococcus pneumoniae with reduced susceptibility to ciprofloxacin in Spain. Antimicrob Agents Chemother 46(8):2665–2667PubMedGoogle Scholar
  77. Philip-Joet F, Bruguerolle B, Reynaud M, Arnaud A (1992) Correlations between theophylline concentrations in plasma, erythrocytes and cantharides-induced blister fluid and peak expiratory flow in asthma patients. Eur J Clin Pharmacol 43(5):563–565PubMedGoogle Scholar
  78. Pien HH, Fischman AJ, Thrall JH, Sorensen AG (2005) Using imaging biomarkers to accelerate drug development and clinical trials. Drug Discov Today 10(4):259–266PubMedGoogle Scholar
  79. Plock N, Kloft C (2005) Microdialysis–theoretical background and recent implementation in applied life-sciences. Eur J Pharm Sci 25(1):1–24PubMedGoogle Scholar
  80. Rea K, Cremers TI, Westerink BH (2005) HPLC conditions are critical for the detection of GABA by microdialysis. J Neurochem 94(3):672–679PubMedGoogle Scholar
  81. Reckziegel R, Maguilnik I, Goldani LZ (2001) Gentamicin concentration in bile after once-daily versus thrice-daily dosing of 4 mg/kg/day. J Antimicrob Chemother 48(2):327–329PubMedGoogle Scholar
  82. Rennard SI, Basset G, Lecossier D, O’Donnell KM, Pinkston P, Martin PG, Crystal RG (1986) Estimation of volume of epithelial lining fluid recovered by lavage using urea as marker of dilution. J Applied Physiol 60(2):532–538Google Scholar
  83. Roberts JA, Lipman J (2009) Pharmacokinetic issues for antibiotics in the critically ill patient. Crit Care Med 37(3): 840–851; quiz 859Google Scholar
  84. Ryan DM (1993) Pharmacokinetics of antibiotics in natural and experimental superficial compartments in animals and humans. J Antimicrob Chemother 31(Suppl D): 1–16Google Scholar
  85. Sahre M, Naik R, Derendorf H (2011) Applications of microdialysis in skin and soft tissues. In: Tsai T-H (ed) Applications of microdialysis in pharmaceutical sciences. Wiley, London, p 584Google Scholar
  86. Sauermann R, Delle-Karth G, Marsik C, Steiner I, Zeitlinger M, Mayer-Helm BX, Georgopoulos A, Muller M, Joukhadar C (2005a) Pharmacokinetics and pharmacodynamics of cefpirome in subcutaneous adipose tissue of septic patients. Antimicrob Agents Chemother 49(2):650–655PubMedGoogle Scholar
  87. Sauermann R, Karch R, Langenberger H, Kettenbach J, Mayer-Helm B, Petsch M, Wagner C, Sautner T, Gattringer R, Karanikas G, Joukhadar C (2005b) Antibiotic abscess penetration: fosfomycin levels measured in pus and simulated concentration-time profiles. Antimicrob Agents Chemother 49(11):4448–4454PubMedGoogle Scholar
  88. Schentag JJ (1989) Clinical significance of antibiotic tissue penetration. Clin Pharmacokinet 16(Suppl 1):25–31PubMedGoogle Scholar
  89. Schmidt S, Banks R, Kumar V, Rand KH, Derendorf H (2008a) Clinical microdialysis in skin and soft tissues: an update. J Clin Pharmacol 48(3):351–364PubMedGoogle Scholar
  90. Schmidt S, Rock K, Sahre M, Burkhardt O, Brunner M, Lobmeyer MT, Derendorf H (2008b) Effect of protein binding on the pharmacological activity of highly bound antibiotics. Antimicrob Agents Chemother 52(11):3994–4000PubMedGoogle Scholar
  91. Schmidt S, Gonzalez D, Derendorf H (2010) Significance of protein binding in pharmacokinetics and pharmacodynamics. J Pharm Sci 99(3):1107–1122PubMedGoogle Scholar
  92. Scott DO, Lunte CE (1993) In vivo microdialysis sampling in the bile, blood, and liver of rats to study the disposition of phenol. Pharm Res 10(3):335–342PubMedGoogle Scholar
  93. Scott DO, Sorensen LR, Lunte CE (1990) In vivo microdialysis sampling coupled to liquid chromatography for the study of acetaminophen metabolism. J Chromatogr 506:461–469PubMedGoogle Scholar
  94. Shandil RK, Jayaram R, Kaur P, Gaonkar S, Suresh BL, Mahesh BN, Jayashree R, Nandi V, Bharath S, Balasubramanian V (2007) Moxifloxacin, ofloxacin, sparfloxacin, and ciprofloxacin against Mycobacterium tuberculosis: evaluation of in vitro and pharmacodynamic indices that best predict in vivo efficacy. Antimicrob Agents Chemother 51(2):576–582PubMedGoogle Scholar
  95. Soman A, Honeybourne D, Andrews J, Jevons G, Wise R (1999) Concentrations of moxifloxacin in serum and pulmonary compartments following a single 400 mg oral dose in patients undergoing fibre-optic bronchoscopy. J Antimicrob Chemother 44(6):835–838PubMedGoogle Scholar
  96. Stenken JA (1999) Methods and issues in microdialysis calibration. Anal Chim Acta 379:337–358Google Scholar
  97. Strenkoski LC, Nix DE (1993) Cefpirome clinical pharmacokinetics. Clin Pharmacokinet 25(4):263–273PubMedGoogle Scholar
  98. Suzuki H, Sawada Y, Sugiyama Y, Iga T, Hanano M (1989) Facilitated transport of benzylpenicillin through the blood-brain barrier in rats. J Pharmacobiodyn 12(3):182–185PubMedGoogle Scholar
  99. Talan DA (2001) Clinical perspectives on new antimicrobials: focus on fluoroquinolones. Clin Infect Dis 32(Suppl 1): S64–S71Google Scholar
  100. Tasso L, Bettoni CC, Oliveira LK, Dalla Costa T (2008) Evaluation of gatifloxacin penetration into skeletal muscle and lung by microdialysis in rats. Int J Pharm 358(1–2):96–101PubMedGoogle Scholar
  101. Taylor AE, Guyton AC, Bishop VS (1965) Permeability of the alveolar membrane to solutes. Circ Res 16:353–362PubMedGoogle Scholar
  102. Thallinger C, Buerger C, Plock N, Kljucar S, Wuenscher S, Sauermann R, Kloft C, Joukhadar C (2008) Effect of severity of sepsis on tissue concentrations of linezolid. J Antimicrob Chemother 61(1):173–176PubMedGoogle Scholar
  103. Thys JP, Vanderhoeft P, Herchuelz A, Bergmann P, Yourassowsky E (1988) Penetration of aminoglycosides in uninfected pleural exudates and in pleural empyemas. Chest 93(3):530–532PubMedGoogle Scholar
  104. Traunmuller F, Schintler MV, Spendel S, Popovic M, Mauric O, Scharnagl E, Joukhadar C (2010) Linezolid concentrations in infected soft tissue and bone following repetitive doses in diabetic patients with bacterial foot infections. Int J Antimicrob Agents 36(1):84–86PubMedGoogle Scholar
  105. Tunblad K, Jonsson EN, Hammarlund-Udenaes M (2003) Morphine blood-brain barrier transport is influenced by probenecid co-administration. Pharm Res 20(4):618–623PubMedGoogle Scholar
  106. Ungerstedt U, Pycock C (1974) Functional correlates of dopamine neurotransmission. Bull Schweiz Akad Med Wiss 30(1–3):44–55PubMedGoogle Scholar
  107. Van Bambeke F, Barcia-Macay M, Lemaire S, Tulkens PM (2006) Cellular pharmacodynamics and pharmacokinetics of antibiotics: current views and perspectives. Curr Opin Drug Discov Devel 9(2):218–230PubMedGoogle Scholar
  108. Wiseman LR, Lamb HM (1997) Cefpirome. A review of its antibacterial activity, pharmacokinetic properties and clinical efficacy in the treatment of severe nosocomial infections and febrile neutropenia. Drugs 54(1):117–140PubMedGoogle Scholar
  109. Wiskirchen DE, Shepard A, Kuti JL, Nicolau DP (2011) Determination of tissue penetration and pharmacokinetics of linezolid in patients with diabetic foot infections using in vivo microdialysis. Antimicrob Agents Chemother 55(9):4170–4175PubMedGoogle Scholar
  110. Xie R, Hammarlund-Udenaes M (1998) Blood-brain barrier equilibration of codeine in rats studied with microdialysis. Pharm Res 15(4):570–575PubMedGoogle Scholar
  111. Zeitlinger M, Muller M, Joukhadar C (2005) Lung microdialysis—a powerful tool for the determination of exogenous and endogenous compounds in the lower respiratory tract (mini-review). Aaps J 7(3): E600–E608Google Scholar
  112. Zeitlinger BS, Zeitlinger M, Leitner I, Muller M, Joukhadar C (2007) Clinical scoring system for the prediction of target site penetration of antimicrobials in patients with sepsis. Clin Pharmacokinet 46(1):75–83PubMedGoogle Scholar
  113. Zeitlinger MA, Derendorf H, Mouton JW, Cars O, Craig WA, Andes D, Theuretzbacher U (2011) Protein binding: do we ever learn? Antimicrob Agents Chemother 55(7):3067–3074PubMedGoogle Scholar
  114. Zhanel GG, Dueck M, Hoban DJ, Vercaigne LM, Embil JM, Gin AS, Karlowsky JA (2001) Review of macrolides and ketolides: focus on respiratory tract infections. Drugs 61(4):443–498PubMedGoogle Scholar
  115. Zhang MY, Beyer CE (2006) Measurement of neurotransmitters from extracellular fluid in brain by in vivo microdialysis and chromatography-mass spectrometry. J Pharm Biomed Anal 40(3):492–499PubMedGoogle Scholar
  116. Zhang MY, Hughes ZA, Kerns EH, Lin Q, Beyer CE (2007) Development of a liquid chromatography/tandem mass spectrometry method for the quantitation of acetylcholine and related neurotransmitters in brain microdialysis samples. J Pharm Biomed Anal 44(2):586–593PubMedGoogle Scholar
  117. Zhang QL, Hu JH, Zhu QG, Li FQ, Liu JY, Wang D (2009) Development of a novel HPLC-MS/MS method for the determination of aconitine and its application to in vitro and rat microdialysis samples. Biomed Chromatogr 23(7):692–699PubMedGoogle Scholar
  118. Zhu Y, Wong PS, Cregor M, Gitzen JF, Coury LA, Kissinger PT (2000) In vivo microdialysis and reverse phase ion pair liquid chromatography/tandem mass spectrometry for the determination and identification of acetylcholine and related compounds in rat brain. Rapid Commun Mass Spectrom 14(18):1695–1700PubMedGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2013

Authors and Affiliations

  • Markus Zeitlinger
    • 1
  • Sandrine Marchand
    • 2
  • William Couet
    • 2
  • Aline Barth
    • 3
  • Hartmut Derendorf
    • 3
  1. 1.Department of Clinical PharmacologyMedical University of ViennaViennaAustria
  2. 2.School of Medicine and PharmacyUniversity of Poitiers, Pharmacologie des Anti-Infectieux, Pôle Biologie SantéPoitiers cedexFrance
  3. 3.Department of PharmaceuticsUniversity of Florida, College of PharmacyGainesvilleUSA

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