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Review of Clinical Pharmacokinetics of Levofloxacin with Special Emphasis in Burn Wound Patients

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Vascular Surgery, Neurosurgery, Lower Extremity Ulcers, Antimicrobials, Wound Assessment, Care, Measurement and Repair

Part of the book series: Recent Clinical Techniques, Results, and Research in Wounds ((RCTRRW,volume 5))

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Abstract

Levofloxacin is a broad-spectrum fluoroquinolone antibiotic, active against a wide variety of pathogens. Levofloxacin exhibits excellent safety and tolerability profile in both healthy subjects and patient population. The focus of the chapter, herein, is on the pharmacokinetics of levofloxacin with emphasis on burn injury patients. In general, levofloxacin showed consistent and stationary pharmacokinetics between single- and multiple-dose administrations. Due to rapid and almost complete oral bioavailability, the pharmacokinetics of intravenous versus oral levofloxacin was similar. The lack of either sex- or age-related difference in the pharmacokinetics of levofloxacin was another distinctive advantage. Similarity in the pharmacokinetics of levofloxacin between intensive care patients and healthy individuals was established. Likewise burn injury was not found to alter the pharmacokinetics of levofloxacin. Since urinary excretion of levofloxacin was a major route of elimination, renal function status was expected to influence the disposition of levofloxacin either in healthy subjects or in patients including burn injury subjects. However, the degree of variability in levofloxacin pharmacokinetics was found to be larger in burn injury patients attributable due to the physiological duress.

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References

  1. Hooper DC (2000) New uses for new and old quinolones and the challenge of resistance. Clin Infect Dis 30(2):243–254

    Article  CAS  PubMed  Google Scholar 

  2. Zhanel GG, Ennis K, Vercaigne L, Walkty A, Gin AS, Embil J, Smith H, Hobon DJ (2002) A critical review of the fluoroquinolones: focus on respiratory infections. Drugs 62(1):13–59

    Article  CAS  PubMed  Google Scholar 

  3. Zhanel GG, Walkty A, Vercaigne L, Karlowsky JA, Embil J, Gin AS, Hoban DJ (1999) The new fluoroquinolones: a critical review. Can J Infect Dis 10:207–238

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. O’Donnell JA, Gelone SP (2000) Fluoroquinolones. Infect Dis Clin North Am 14:489–513

    Article  PubMed  Google Scholar 

  5. Srinivas NR (2016) Predictions of the pharmacokinetics in burn injury patients using regression models - case study with levofloxacin. Drug Res (Stuttg) 66(10):555–560

    Article  CAS  Google Scholar 

  6. Kiser TH, Hoody DW, Obritsch MD, Wegzyn CO, Bauling PC, Fish DN (2006) Levofloxacin pharmacokinetics and pharmacodynamics in patients with severe burn injury. Antimicrob Agents Chemother 50(6):1937–1945

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Jaehde U, Sorge F (1995) Clinical pharmacokinetics in patients with burns. Clin Pharmacokinet 29(1):15–28

    Article  CAS  PubMed  Google Scholar 

  8. Epstein MD, Tchervenkov JI, Alexander JW, Johnson JR, Vester JW (1991) Increased gut permeability following bum trauma. Arch Surg 126:198–200

    Article  CAS  PubMed  Google Scholar 

  9. Zini R, Riant P, Barre J, Tillement JP (1990) Disease-induced variations in plasma protein levels. Implications for drug dosage regimens (part 1). Clin Pharmacokinet 19(2):147–159

    Article  CAS  PubMed  Google Scholar 

  10. Rowland M, Tozer TN (1989) Clinical pharmacokinetics: concepts and applications. Lea &Febiger, Philadelphia, pp 145–146. 187–8

    Google Scholar 

  11. Garrelts JC, Jost G, Kowalsky SF, Krol GJ, Lettieri JT (1996) Ciprofloxacin pharmacokinetics in burn patients. Antimicrob Agents Chemother 40:1153–1156

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Garrelts JC, Peterie JD (1988) Altered vancomycin dose vs. serum concentration relationship in burn patients. Clin Pharmacol Ther 44:9–13

    Article  CAS  PubMed  Google Scholar 

  13. Zaske DE, Sawchuk RJ, Gerding DN, Strate RG (1976) Increased dosage requirements of gentamicin in burn patients. J Trauma 16:824–828

    Article  CAS  PubMed  Google Scholar 

  14. Zaske DE, Sawchuk RJ, Strate RG (1978) The necessity of increased doses of amikacin in burn patients. Surgery 84:603–608

    CAS  PubMed  Google Scholar 

  15. Chow AT, Fowler C, Williams RR, Morgan N, Kaminski S, Natarajan J (2001) Safety and pharmacokinetics of multiple 750-milligram doses of intravenous levofloxacin in healthy volunteers. Antimicrob Agents Chemother 45(7):2122–2125

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Zhang L, Li JT, Lu Y, Li MN, Zhang YL, Liu Y, Li TY, Zhang JW (2002) Pharmacokinetics of multiple intravenous instillation of levofloxacin in Chinese healthy subjects. Acta Pharmacol Sin 23(4):381–384

    CAS  PubMed  Google Scholar 

  17. Nakashima M, Uematsu T, Kanamaru M, Okazaki O, Hakusui H (1992) Phase I study of levofloxacin, (S)-(-)-ofloxacin. Jpn J Clin Pharmacol Ther 23(2):515–520

    Article  CAS  Google Scholar 

  18. Madhavi M, Priyanka UM (2014) Influence of follicular and luteal phase on levofloxacin pharmacokinetics in female volunteers. Int J Pharm Bio Sci 5(1):305–312

    CAS  Google Scholar 

  19. Abuelkheir MM (2009) Effect of pharmacokinetic differences between men and women on pharmacodynamic target attainment of levofloxacin against Streptococcus pneumoniae. Saudi Pharm J 17(1):29–39

    CAS  Google Scholar 

  20. Thee S, Garcia-Prats AJ, McIlleron HM, Wiesner L, Castel S, Norman J, Draper HR, van der Merwe PL, Hesseling AC, Schaaf HS (2014) Pharmacokinetics of ofloxacin and levofloxacin for prevention and treatment of multidrug-resistant tuberculosis in children. Antimicrob Agents Chemother 58(5):2948–2951

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Trampuz A, Wenk M, Rajacic Z, Zimmerli W (2000) Pharmacokinetics and pharmacodynamics of levofloxacin against Streptococcus pneumoniae and Staphylococcus aureus in human skin blister fluid. Antimicrob Agents Chemother 44(5):1352–1355

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Chow AT, Chen A, Lattime H, Morgan N, Wong F, Fowler C, Williams RR (2002) Penetration of levofloxacin into skin tissue after oral administration of multiple 750 mg once-daily doses. J Clin Pharm Ther 27(2):143–150

    Article  CAS  PubMed  Google Scholar 

  23. Child J, Mortiboy D, Andrews JM, Chow AT, Wise R (1995) Open-label crossover study to determine pharmacokinetics and penetration of two dose regimens of levofloxacin into inflammatory fluid. Antimicrob Agents Chemother 39(12):2749–2751

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Benko R, Matuz M, Doro P, Peto Z, Molnar A, Hajdu E, Nagy E, Gardi J, Soos G (2007) Pharmacokinetics and pharmacodynamics of levofloxacin in critically ill patients with ventilator-associated pneumonia. Int J Antimicrob Agents 30(2):162–168

    Article  CAS  PubMed  Google Scholar 

  25. Boselli E, Breilh D, Rimmelé T, Djabarouti S, Saux MC, Chassard D, Allaouchiche B (2005) Pharmacokinetics and intrapulmonary diffusion of levofloxacin in critically ill patients with severe community-acquired pneumonia. Crit Care Med 33(1):104–109

    Article  CAS  PubMed  Google Scholar 

  26. Furlanut M, Brollo L, Lugatti E, Di Qual E, Dolcet F, Talmassons G, Pea F (2003) Pharmacokinetic aspects of levofloxacin 500 mg once daily during sequential intravenous/oral therapy in patients with lower respiratory tract infections. J Antimicrob Chemother 51(1):101–106

    Article  CAS  PubMed  Google Scholar 

  27. Lubasch A, Keller I, Borner K, Koeppe P, Lode H (2000) Comparative pharmacokinetics of ciprofloxacin, gatifloxacin, grepafloxacin, levofloxacin, trovafloxacin, and moxifloxacin after single oral administration in healthy volunteers. Antimicrob Agents Chemother 44(10):2600–2603

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Noreddin AM, Marras TK, Sanders K, Chan CK, Hoban DJ, Zhanel GG (2004) Pharmacodynamic target attainment analysis against Streptococcus pneumoniae using levofloxacin 500 mg, 750 mg and 1000 mg once daily in plasma (P) and epithelial lining fluid (ELF) of hospitalized patients with community acquired pneumonia (CAP). Int J Antimicrob Agents 24(5):479–484

    Article  CAS  PubMed  Google Scholar 

  29. Pea F, Di Qual E, Cusenza A, Brollo L, Baldassarre M, Furlanut M (2003) Pharmacokinetics and pharmacodynamics of intravenous levofloxacin in patients with early-onset ventilator-associated pneumonia. Clin Pharmacokinet 42(6):589–598

    Article  CAS  PubMed  Google Scholar 

  30. Bellmann R, Kuchling G, Dehghanyar P, Zeitlinger M, Minar E, Mayer BX, Müller M, Joukhadar C (2004) Tissue pharmacokinetics of levofloxacin in human soft tissue infections. Br J Clin Pharmacol 57(5):563–568

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Geller DE, Flume PA, Griffith DC, Morgan E, White D, Loutit JS, Dudley MN (2011) Pharmacokinetics and safety of MP-376 (levofloxacin inhalation solution) in cystic fibrosis subjects. Antimicrob Agents Chemother 55(6):2636–2640

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Lee CK, Boyle MP, Diener-West M, Brass-Ernst L, Noschese M, Zeitlin PL (2007) Levofloxacin pharmacokinetics in adult cystic fibrosis. Chest 131(3):796–802

    Article  CAS  PubMed  Google Scholar 

  33. Rebuck JA, Fish DN, Abraham E (2002) Pharmacokinetics of intravenous and oral levofloxacin in critically ill adults in a medical intensive care unit. Pharmacotherapy 22(10):1216–1225

    Article  CAS  PubMed  Google Scholar 

  34. Drusano GL, Preston SL, Van Guilder M, North D, Gombert M, Oefelein M, Boccumini L, Weisinger B, Corrado M, Kahn J (2000) A population pharmacokinetic analysis of the penetration of the prostate by levofloxacin. Antimicrob Agents Chemother 44(8):2046–2051

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Goodwin SD, Gallis HA, Chow AT, Wong FA, Flor SC, Bartlett JA (1994) Pharmacokinetics and safety of levofloxacin in patients with human immunodeficiency virus infection. Antimicrob Agents Chemother 38(4):799–804

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Piscitelli SC, Spooner K, Baird B, Chow AT, Fowler CL, Williams RR, Natarajan J, Masur H, Walker RE (1999) Pharmacokinetics and safety of high-dose and extended-interval regimens of levofloxacin in human immunodeficiency virus-infected patients. Antimicrob Agents Chemother 43(9):2323–2327

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Hutschala D, Skhirtladze K, Zuckermann A, Wisser W, Jaksch P, Mayer-Helm BX, Burgmann H, Wolner E, Müller M, Tschernko EM (2005) In vivo measurement of levofloxacin penetration into lung tissue after cardiac surgery. Antimicrob Agents Chemother 49(12):5107–5111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Usman M, Ashraf M, Khokhar MI, Ashiq B, Masood MI, Afzal S, Omer O, Ali M, Qadir MI (2013) Comparative pharmacokinetics of levofloxacin in healthy volunteers and in patients suffering from typhoid Fever. Iran J Pharm Res 12(1):147–154

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Weinrich M, Scheingraber S, Stremovskaia T, Schilling MK, Kees F, Pistorius GA (2006) Liver tissue concentrations of levofloxacin after single intravenous administration of 500 mg for antibiotic prophylaxis in liver surgery. Int J Antimicrob Agents 28(3):221–225

    Article  CAS  PubMed  Google Scholar 

  40. Bellmann R, Egger P, Gritsch W, Bellmann-Weiler R, Joannidis M, Dunzendorfer S, Wiedermann CJ (2002) Elimination of levofloxacin in critically ill patients with renal failure: influence of continuous veno-venous hemofiltration. Int J Clin Pharmacol Ther 40(4):142–149

    Article  CAS  PubMed  Google Scholar 

  41. Malone RS, Fish DN, Abraham E, Teitelbaum I (2001) Pharmacokinetics of levofloxacin and ciprofloxacin during continuous renal replacement therapy in critically ill patients. Antimicrob Agents Chemother 45(10):2949–2954

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Sowinski KM, Lucksiri A, Kays MB, Scott MK, Mueller BA, Hamburger RJ (2003) Levofloxacin pharmacokinetics in ESRD and removal by the cellulose acetate high performance-210 hemodialyzer. Am J Kidney Dis 42(2):342–349

    Article  CAS  PubMed  Google Scholar 

  43. Nicolle L, Duckworth H, Sitar D, Bryski L, Harding G, Zhanel G (2008) Pharmacokinetics/pharmacodynamics of levofloxacin 750 mg once daily in young women with acute uncomplicated pyelonephritis. Int J Antimicrob Agents 31(3):287–289

    Article  CAS  PubMed  Google Scholar 

  44. Tsaganos T, Kouki P, Digenis P, Giamarellou H, Giamarellos-Bourboulis EJ, Kanellakopoulou K (2008) Pharmacokinetics of levofloxacin after single and multiple oral doses in patients undergoing intermittent haemodialysis. Int J Antimicrob Agents 32(1):46–49

    Article  CAS  PubMed  Google Scholar 

  45. Guenter SG, Iven H, Boos C, Bruch HP, Muhl E (2002) Pharmacokinetics of levofloxacin during continuous venovenous hemodiafiltration and continuous venovenous hemofiltration in critically ill patients. Pharmacotherapy 22(2):175–183

    Article  CAS  PubMed  Google Scholar 

  46. Chien SC, Chow AT, Rogge MC, Williams RR, Hendrix CW (1997) Pharmacokinetics and safety of oral levofloxacin in human immunodeficiency virus-infected individuals receiving concomitant zidovudine. Antimicrob Agents Chemother 41(8):1765–1769

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Fish DN, Chow AT (1997) The clinical pharmacokinetics of levofloxacin. Clin Pharmacokinet 32(2):101–119

    Article  CAS  PubMed  Google Scholar 

  48. Conte JE Jr, Golden JA, McIver M, Little E, Zurlinden E (2007) Intrapulmonary pharmacodynamics of high-dose levofloxacin in subjects with chronic bronchitis or chronic obstructive pulmonary disease. Int J Antimicrob Agents 30(5):422–427

    Article  CAS  PubMed  Google Scholar 

  49. Kempker RR, Barth AB, Vashakidze S, Nikolaishvili K, Sabulua I, Tukvadze N, Bablishvili N, Gogishvili S, Singh RS, Guarner J, Derendorf H, Peloquin CA, Blumberg HM (2015) Cavitary penetration of levofloxacin among patients with multidrug-resistant tuberculosis. Antimicrob Agents Chemother 59(6):3149–3155

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Lee LJ, Hafkin B, Lee ID, Hoh J, Dix R (1997) Effects of food and sucralfate on a single oral dose of 500 milligrams of levofloxacin in healthy subjects. Antimicrob Agents Chemother 41(10):2196–2200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Radandt JM, Marchbanks CR, Dudley MN (1992) Interactions of fluoroquinolones with other drugs: mechanisms, variability, clinical significance, and management. Clin Infect Dis 14:272–284

    Article  CAS  PubMed  Google Scholar 

  52. Okimoto N, Niki Y, Soejima R (1992) Effect of levofloxacin on serum concentration of theophylline. Chemotherapy 40(Suppl 3):68–74

    CAS  Google Scholar 

  53. Shiba K, Sakai O, Shimada J, Okazaki O, Aoki H, Hakusui H (1992) Effect of antacids, ferrous sulfate, and ranitidine on absorption of DR-3355 in humans. Antimicrob Agents Chemother 36:2270–2274

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Gaitonde MD, Mendes P, House ESA, Lehr KH (1995) The effects of cimetidine and probenecid on the pharmacokinetics of levofloxacin [abstract no. A41]. American Society for Microbiology: Abstracts of the 35th Interscience Conference on Antimicrobial Agents and Chemotherapy, 35; 8

    Google Scholar 

  55. Sánchez Navarro A, Colino Gandarillas CI, Alvarez Lerma F, Menacho YA, Domínguez-Gil A (2005) Pharmacokinetics and pharmacodynamics of levofloxacin in intensive care patients. Clin Pharmacokinet 44(6):627–635

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Johns Hopkins Drug Discovery Program, Johns Hopkins University, Baltimore, MD, USA

    Ranjeet Prasad Dash & Rana Rais

  2. Department of Neurology, Johns Hopkins University, Baltimore, MD, USA

    Ranjeet Prasad Dash & Rana Rais

  3. Zydus Research Centre, Ahmedabad, Gujarat, India

    Nuggehally R. Srinivas

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  1. Ranjeet Prasad Dash
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  2. Rana Rais
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Correspondence to Nuggehally R. Srinivas .

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  1. Tustin, CA, USA

    Melvin A. Shiffman

  2. Newport Beach, CA, USA

    Mervin Low

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Dash, R.P., Rais, R., Srinivas, N.R. (2018). Review of Clinical Pharmacokinetics of Levofloxacin with Special Emphasis in Burn Wound Patients. In: Shiffman, M., Low, M. (eds) Vascular Surgery, Neurosurgery, Lower Extremity Ulcers, Antimicrobials, Wound Assessment, Care, Measurement and Repair. Recent Clinical Techniques, Results, and Research in Wounds, vol 5. Springer, Cham. https://doi.org/10.1007/15695_2017_80

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  • DOI: https://doi.org/10.1007/15695_2017_80

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  • Print ISBN: 978-3-030-10715-4

  • Online ISBN: 978-3-030-10716-1

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