European Journal of Clinical Pharmacology

, Volume 69, Issue 7, pp 1351–1368

Role of diuretics and lipid formulations in the prevention of amphotericin B-induced nephrotoxicity

  • Iman Karimzadeh
  • Hossein Khalili
  • Shadi Farsaei
  • Simin Dashti-Khavidaki
  • Mohammad Mahdi Sagheb
Review Article



To collect available clinical data to define the role of diuretics and lipid formulations in the prevention of amphotericin B (AmB)-induced nephrotoxicity (AIN) in human populations.


A literature search was performed in the following databases: Scopus, Medline, Embase, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews.

Results and conclusion

Co-administration of mannitol failed to show any clinically significant benefit in preventing AIN. Potassium-sparing diuretics, such as amiloride and spironolactone, have been shown to have beneficial effects as an alternative or adjunct to oral/parenteral potassium supplements in preventing hypokalemia due to AmB. Lipid-based formulations of AmB are clinically effective and safe in preventing AIN. However, due to their high cost and limited accessibility, these formulations are generally used as second-line antifungal therapy in cases of conventional AmB refractoriness and/or intolerance or pre-existing renal dysfunction. The potential effects of other nephroprotective agents, such as N-acetylcysteine, AIN merit further considerations and investigations.


Amphotericin Nephrotoxicity Prevention 


  1. 1.
    Laniado-Laborín R, Cabrales-Vargas MN (2009) Amphotericin B: side effects and toxicity. RevI beroam Micol 26:223–227CrossRefGoogle Scholar
  2. 2.
    Ulozas E (2010) Amphotericin B-induced nephrotoxicity. Compr Toxicol 7:347–357CrossRefGoogle Scholar
  3. 3.
    Gallis HA, Drew RH, Pickard WW (1990) Amphotericin B: 30 years of clinical experience. Rev Infect Dis 12:308–329PubMedCrossRefGoogle Scholar
  4. 4.
    Anderson CM (1995) Sodium chloride treatment of amphotericin B nephrotoxicity-standard of care? West J Med 162:313–317PubMedGoogle Scholar
  5. 5.
    Harbarth S, Pestotnik SL, Lloyd JF, Burke JP, Samore MH (2001) The epidemiology of nephrotoxicity associated with conventional amphotericin B therapy. Am J Med 111:528–534PubMedCrossRefGoogle Scholar
  6. 6.
    Fanos V, Cataldi L (2000) Amphotericin B-induced nephrotoxicity: a review. J Chemother 12(6):463–470PubMedGoogle Scholar
  7. 7.
    Goldman RD, Koren G (2004) Amphotericin B nephrotoxicity in children. J Pediatr Hematol Oncol 26:421–426PubMedCrossRefGoogle Scholar
  8. 8.
    Atsmon J, Dolev E (2005) Drug-induced hypomagnesaemia: scope and management. Drug Saf 28:763–788PubMedCrossRefGoogle Scholar
  9. 9.
    Llanos A, Cieza J, Bernardo J et al (1991) Effect of salt supplementation on amphotericin B nephrotoxicity. Kidney Int 40:302–308PubMedCrossRefGoogle Scholar
  10. 10.
    Wazny LD, Brophy DF (2000) Amiloride for the prevention of amphotericin B-induced hypokalemia and hypomagnesemia. Ann Pharmacother 34:94–97PubMedCrossRefGoogle Scholar
  11. 11.
    Bates DW, Su L, Yu DT et al (2001) Mortality and costs of acute renal failure associated with amphotericin B therapy. Clin Infect Dis 32:686–693PubMedCrossRefGoogle Scholar
  12. 12.
    Karimzadeh I, Farsaei S, Khalili H, Dashti-Khavidaki S (2012) Are salt loading and prolonging infusion period effective in prevention of amphotericin B-induced nephrotoxicity? Expert Opin Drug Saf 11:969–983PubMedCrossRefGoogle Scholar
  13. 13.
    Venkataraman R, Kellum JA (2007) Prevention of acute renal failure. Chest 131:300–308PubMedCrossRefGoogle Scholar
  14. 14.
    Nigwekar SU, Waikar SS (2011) Diuretics in acute kidney injury. Semin Nephrol 31:523–534PubMedCrossRefGoogle Scholar
  15. 15.
    Hellebusch AA, Salama F, Eadie E (1972) The use of mannitol to reduce the nephrotoxicity of amphotericin B. Surg Gynecol Obstet 134:241–243PubMedGoogle Scholar
  16. 16.
    Rosch JM, Pazin GJ, Fireman P (1976) Reduction of amphotericin B nephrotoxicity with mannitol. JAMA 235:1995–1996PubMedCrossRefGoogle Scholar
  17. 17.
    Olivero JJ, Lozano-Mendez J, Ghafary EM, Eknoyan G, Suki WN (1975) Mitigation of amphotericin B nephrotoxicity by mannitol. Br Med J 1:550–551PubMedCrossRefGoogle Scholar
  18. 18.
    Bullock WE, Luke RG, Nuttall CE, Bhathena D (1976) Can mannitol reduce amphotericin B nephrotoxicity? Double-blind study and description of a new vascular lesion in kidneys. Antimicrob Agents Chemother 10:555–563PubMedCrossRefGoogle Scholar
  19. 19.
    Cvitkovic E, Spaulding J, Bethune V, Martin J, Whitmore WF (1977) Improvement of cis-dichlorodiammineplatinum (NSC 119875): therapeutic index in an animal model. Cancer 39:1357–1361PubMedCrossRefGoogle Scholar
  20. 20.
    Al-Sarraf M, Fletcher W, Oishi N, Pugh R, Hewlett JS, Balducci L, McCracken J, Padilla F (1982) Cisplatin hydration with and without mannitol diuresis in refractory disseminated malignant melanoma: a southwest oncology group study. Cancer Treat Rep 66:31–35PubMedGoogle Scholar
  21. 21.
    Smith SR, Galloway MJ, Reilly JT, Davies JM (1988) Amiloride prevents amphotericin B related hypokalaemia in neutropenic patients. J Clin Pathol 41:494–497PubMedCrossRefGoogle Scholar
  22. 22.
    Bearden DT, Muncey LA (2001) The effect of amiloride on amphotericin B-induced hypokalaemia. J Antimicrob Chemother 48:109–111PubMedCrossRefGoogle Scholar
  23. 23.
    Epstein M, Calhoun DA (2011) Aldosterone blockers (mineralocorticoid receptor antagonism) and potassium-sparing diuretics. J Clin Hypertens (Greenwich) 13:644–648CrossRefGoogle Scholar
  24. 24.
    Ural AU, Avcu F, Cetin T, Beyan C, Kaptan K, Nazaroglu NK, Yalcin A (2002) Spironolactone: is it a novel drug for the prevention of amphotericin B-related hypokalemia in cancer patients? Eur J Clin Pharmacol 57:771–773PubMedCrossRefGoogle Scholar
  25. 25.
    Hippalgaonkar K, Majumdar S, Kansara V (2010) Injectable lipid emulsions-advancements, opportunities and challenges. AAPS PharmSciTech 11:1526–1540PubMedCrossRefGoogle Scholar
  26. 26.
    Kirsh R, Goldstein R, Tarloff J, Parris D, Hook J, Hanna N, Bugelski P, Poste G (1988) An emulsion formulation of amphotericin B improves the therapeutic index when treating systemic murine candidiasis. J Infect Dis 158:1065–1070PubMedCrossRefGoogle Scholar
  27. 27.
    Moreau P, Milpied N, Fayette N, Ramée JF, Harousseau JL (1992) Reduced renal toxicity and improved clinical tolerance of amphotericin B mixed with intralipid compared with conventional amphotericin B in neutropenic patients. J Antimicrob Chemother 30:535–541PubMedCrossRefGoogle Scholar
  28. 28.
    Pascual B, Ayestaran A, Montoro JB, Oliveras J, Estibalez A, Julia A, Lopez A (1995) Administration of lipid-emulsion versus conventional amphotericin B in patients with neutropenia. Ann Pharmacother 29:1197–1201PubMedGoogle Scholar
  29. 29.
    Caillot D, Casasnovas O, Solary E, Chavanet P, Bonnotte B, Reny G, Entezam F, Lopez J, Bonnin A, Guy H (1993) Efficacy and tolerance of an amphotericin B lipid (Intralipid) emulsion in the treatment of candidaemia in neutropenic patients. J Antimicrob Chemother 31:161–169PubMedCrossRefGoogle Scholar
  30. 30.
    Schöffski P, Freund M, Wunder R, Petersen D, Köhne CH, Hecker H, Schubert U, Ganser A (1998) Safety and toxicity of amphotericin B in glucose 5 % or intralipid 20 % in neutropenic patients with pneumonia or fever of unknown origin: randomised study. Br Med J 317:379–384CrossRefGoogle Scholar
  31. 31.
    Caillot D, Reny G, Solary E, Casasnovas O, Chavanet P, Bonnotte B, Perello L, Dumas M, Entezam F, Guy H (1994) A controlled trial of the tolerance of amphotericin B infused in dextrose or in Intralipid in patients with haematological malignancies. J Antimicrob Chemother 33:603–613PubMedCrossRefGoogle Scholar
  32. 32.
    Nucci M, Loureiro M, Silveira F, Casali AR, Bouzas LF, Velasco E, Spector N, Pulcheri W (1999) Comparison of the toxicity of amphotericin B in 5 % dextrose with that of amphotericin B in fat emulsion in a randomized trial with cancer patients. Antimicrob Agents Chemother 43:1445–1448PubMedGoogle Scholar
  33. 33.
    Nath CE, Shaw PJ, Gunning R, McLachlan AJ, Earl JW (1999) Amphotericin B in children with malignant disease: a comparison of the toxicities and pharmacokinetics of amphotericin B administered in dextrose versus lipid emulsion. Antimicrob Agents Chemother 43:1417–1423PubMedGoogle Scholar
  34. 34.
    Trissel LA (1995) Amphotericin B does not mix with fat emulsion. Am J Health Syst Pharm 52:1463–1464PubMedGoogle Scholar
  35. 35.
    Chavanet PY, Garry I, Charlier N, Caillot D, Kisterman JP, D’Athis M, Portier H (1992) Trial of glucose versus fat emulsion in preparation of amphotericin for use in HIV infected patients with candidiasis. Br Med J 305:921–925CrossRefGoogle Scholar
  36. 36.
    Chavanet P, Clement C, Duong M, Buisson M, D’Athis P, Dumas M, Bonnin A, Portier H (1997) Toxicity and efficacy of conventional amphotericin B deoxycholate versus escalating doses of amphotericin B deoxycholate-fat emulsion in HIV-infected patients with oral candidosis. Clin Microbiol Infect 3:455–461PubMedCrossRefGoogle Scholar
  37. 37.
    Joly V, Aubry P, Ndayiragide A, Carrière I, Kawa E, Mlika-Cabanne N, Aboulker JP, Coulaud JP, Larouze B, Yeni P (1996) Randomized comparison of amphotericin B deoxycholate dissolved in dextrose or Intralipid for the treatment of AIDS-associated cryptococcal meningitis. Clin Infect Dis 23:556–562PubMedCrossRefGoogle Scholar
  38. 38.
    Sorkine P, Nagar H, Weinbroum A, Setton A, Israitel E, Scarlatt A, Silbiger A, Rudick V, Kluger Y, Halpern P (1996) Administration of amphotericin B in lipid emulsion decreases nephrotoxicity: results of a prospective, randomized, controlled study in critically ill patients. Crit Care Med 24:1311–1315PubMedCrossRefGoogle Scholar
  39. 39.
    Barquist E, Fein E, Shadick D, Johnson J, Clark J, Shatz D (1999) A randomized prospective trial of amphotericin B lipid emulsion versus dextrose colloidal solution in critically ill patients. J Trauma 47:336–340PubMedCrossRefGoogle Scholar
  40. 40.
    Thakur CP (1994) Comparison of glucose versus fat emulsion in the preparation of amphotericin B for use in kala-azar. Trans R Soc Trop Med Hyg 88:698–699PubMedCrossRefGoogle Scholar
  41. 41.
    Sundar S, Chakravarty J, Agarwal D, Shah A, Agrawal N, Rai M (2008) Safety of a pre-formulated amphotericin B lipid emulsion for the treatment of Indian Kala-azar. Trop Med Int Health 13:1208–1212PubMedCrossRefGoogle Scholar
  42. 42.
    Sundar S, Singh A, Agarwal D, Rai M, Agrawal N, Chakravarty J (2009) Safety and efficacy of high-dose infusions of a preformed amphotericin B fat emulsion for treatment of Indian visceral leishmaniasis. Am J Trop Med Hyg 80:700–703PubMedGoogle Scholar
  43. 43.
    Salama S, Rotstein C (1997) Reduction in the nephrotoxicity of amphotericin B when administered in 20 % intralipid. Can J Infect Dis 8:157–160PubMedGoogle Scholar
  44. 44.
    Anderson RP, Clark DA (1995) Amphotericin B toxicity reduced by administration in fat emulsion. Ann Pharmacother 29:496–500PubMedGoogle Scholar
  45. 45.
    Mistro S, Maciel Ide M, de Menezes RG, Maia ZP, Schooley RT, Badaró R (2012) Does lipid emulsion reduce amphotericin B nephrotoxicity? A systematic review and meta-analysis. Clin Infect Dis 54:1774–1777PubMedCrossRefGoogle Scholar
  46. 46.
    Ericsson O, Hallmen AC, Wikstrom I (1996) Amphotericin B is incompatible with lipid emulsions. Ann Pharmacother 30:298PubMedGoogle Scholar
  47. 47.
    Cleary JD (1996) Amphotericin B formulated in a lipid emulsion. Ann Pharmacother 30:409–412PubMedGoogle Scholar
  48. 48.
    Heide PE (1997) Precipitation of amphotericin B from i.v. fat emulsion. Am J Health Syst Pharm 54:1449PubMedGoogle Scholar
  49. 49.
    National Library of Medicine, National Institutes of Health. Intralipid (soybean oil) emulsion. Available at: = 6275. Accessed 4 May 2012
  50. 50.
    Johnson RH, Einstein HE (2007) Amphotericin B and coccidioidomycosis. Ann N Y Acad Sci 1111:434–441PubMedCrossRefGoogle Scholar
  51. 51.
    Kobayashi GS, Little JR, Medoff G (1985) In vitro and in vivo comparisons of amphotericin B and N-D-ornithyl amphotericin B methyl ester. Antimicrob Agents Chemother 27:302–305PubMedCrossRefGoogle Scholar
  52. 52.
    BanghamA D, Hill MW, Miller NGA (1974) Preparationa nd use of liposomes as models of biological membranes. In: KornE D (ed) Methods in membrane biology, vol 1. Plenum Press, New York, pp 1–68CrossRefGoogle Scholar
  53. 53.
    White MH, Bowden RA, Sandler ES, Graham ML, Noskin GA, Wingard JR, Goldman M, van Burik JA, McCabe A, Lin JS, Gurwith M, Miller CB (1998) Randomized, double-blind clinical trial of amphotericin B colloidal dispersion vs. amphotericin B in the empirical treatment of fever and neutropenia. Clin Infect Dis 27:296–302PubMedCrossRefGoogle Scholar
  54. 54.
    White MH, Anaissie EJ, Kusne S, Wingard JR, Hiemenz JW, Cantor A, Gurwith M, Du Mond C, Mamelok RD, Bowden RA (1997) Amphotericin B colloidal dispersion vs. amphotericin B as therapy for invasive aspergillosis. Clin Infect Dis 24:635–642PubMedGoogle Scholar
  55. 55.
    Slain D (1999) Lipid-based amphotericin B for the treatment of fungal infections. Pharmacotherapy 19:306–323PubMedCrossRefGoogle Scholar
  56. 56.
    Mehta R, Lopez-Berestein G, Hopfer R, Mills K, Juliano RL (1984) Liposomal amphotericin B is toxic to fungal cells but not to mammalian cells. Biochim Biophys Acta 770:230–234PubMedCrossRefGoogle Scholar
  57. 57.
    Proffitt RT, Satorius A, Chiang SM, Sullivan L, Adler-Moore JP (1991) Pharmacology and toxicology of a liposomal formulation of amphotericin B (AmBisome) in rodents. J Antimicrob Chemother 28[Suppl B]:49–61PubMedCrossRefGoogle Scholar
  58. 58.
    Lee JW, Amantea MA, Francis PA, Navarro EE, Bacher J, Pizzo PA, Walsh TJ (1994) Pharmacokinetics and safety of a unilamellar liposomal formulation of amphotericin B (AmBisome) in rabbits. Antimicrob Agents Chemother 38:713–718PubMedCrossRefGoogle Scholar
  59. 59.
    Wasan KM, Rosenblum MG, Cheung L, Lopez-Berestein G (1994) Influence of lipoproteins on renal cytotoxicity and antifungal activity of amphotericin B. Antimicrob Agents Chemother 38:223–227PubMedCrossRefGoogle Scholar
  60. 60.
    Perkins WR, Minchey SR, Boni LT, Swenson CE, Popescu MC, Pasternack RF, Janoff AS (1992) Amphotericin B-phospholipid interactions responsible for reduced mammalian cell toxicity. Biochim Biophys Acta 1107:271–282PubMedCrossRefGoogle Scholar
  61. 61.
    Prentice HG, Hann IM, Herbrecht R, Aoun M, Kvaloy S, Catovsky D, Pinkerton CR, Schey SA, Jacobs F, Oakhill A, Stevens RF, Darbyshire PJ, Gibson BE (1997) A randomized comparison of liposomal versus conventional amphotericin B for the treatment of pyrexia of unknown origin in neutropenic patients. Br J Haematol 98:711–718PubMedCrossRefGoogle Scholar
  62. 62.
    Leenders AC, Daenen S, Jansen RL, Hop WC, Lowenberg B, Wijermans PW, Cornelissen J, Herbrecht R, van der Lelie H, Hoogsteden HC, Verbrugh HA, de Marie S (1998) Liposomal amphotericin B compared with amphotericin B deoxycholate in the treatment of documented and suspected neutropenia-associated invasive fungal infections. Br J Haematol 103:205–212PubMedCrossRefGoogle Scholar
  63. 63.
    Walsh TJ, Finberg RW, Arndt C et al (1999) Liposomal amphotericin B for empirical therapy in patients with persistent fever and neutropenia. N Engl J Med 340:764–771PubMedCrossRefGoogle Scholar
  64. 64.
    Johnson PC, Wheat LJ, Cloud GA, Goldman M, Lancaster D, Bamberger DM, Powderly WG, Hafner R, Kauffman CA, Dismukes WE, U.S. National Institute of Allergy and Infectious Diseases Mycoses Study Group (2002) Safety and efficacy of liposomal amphotericin B compared with conventional amphotericin B for induction therapy of histoplasmosis in patients with AIDS. Ann Intern Med 137:105–109PubMedCrossRefGoogle Scholar
  65. 65.
    Sharkey PK, Graybill JR, Johnson ES, Hausrath SG, Pollard RB, Kolokathis A, Mildvan D, Fan-Havard P, Eng RH, Patterson TF, Pottage JC Jr, Simberkoff MS, Wolf J, Meyer RD, Gupta R, Lee LW, Gordon DS (1996) Amphotericin B lipid complex compared with amphotericin B in the treatment of cryptococcal meningitis in patients with AIDS. Clin Infect Dis 22:315–321PubMedCrossRefGoogle Scholar
  66. 66.
    Clark JM, Whitney RR, Olsen SJ, George RJ, Swerdel MR, Kunselman L, Bonner DP (1991) Amphotericin B lipid complex therapy of experimental fungal infections in mice. Antimicrob Agents Chemother 35:615–621PubMedCrossRefGoogle Scholar
  67. 67.
    Coker RJ, Viviani M, Gazzard BG, Du Pont B, Pohle HD, Murphy SM, Atouguia J, Champalimaud JL, Harris JR (1993) Treatment of cryptococcosis with liposomal amphotericin B (AmBisome) in 23 patients with AIDS. AIDS 7:829–835PubMedCrossRefGoogle Scholar
  68. 68.
    Subirà M, Martino R, Gómez L, Martí JM, Estany C, Sierra J (2004) Low-dose amphotericin B lipid complex vs. conventional amphotericin B for empirical antifungal therapy of neutropenic fever in patients with hematologic malignancies–a randomized, controlled trial. Eur J Haematol 72:342–347PubMedCrossRefGoogle Scholar
  69. 69.
    Malani PN, Depestel DD, Riddell J, Bickley S, Klein LR, Kauffman CA (2005) Experience with community-based amphotericin B infusion therapy. Pharmacotherapy 25:690–697PubMedCrossRefGoogle Scholar
  70. 70.
    Ullmann AJ, Sanz MA, Tramarin A, Barnes RA, Wu W, Gerlach BA, Krobot KJ, Gerth WC, Longitudinal Evaluation of Antifungal Drugs (LEAD I) Investigators (2006) Prospective study of amphotericin B formulations in immunocompromised patients in 4 European countries. Clin Infect Dis 43:e29–e38PubMedCrossRefGoogle Scholar
  71. 71.
    Clark AD, McKendrick S, Tansey PJ, Franklin IM, Chopra R (1998) A comparative analysis of lipid-complexed and liposomal amphotericin B preparations in haematological oncology. Br J Haematol 103:198–204PubMedCrossRefGoogle Scholar
  72. 72.
    Wingard JR, White MH, Anaissie E, Raffalli J, Goodman J, Arrieta A, L Amph/ABLC Collaborative Study Group (2000) A randomized, double-blind comparative trial evaluating the safety of liposomal amphotericin B versus amphotericin B lipid complex in the empirical treatment of febrile neutropenia. L Amph/ABLC Collaborative Study Group. Clin Infect Dis 31:1155–1163PubMedCrossRefGoogle Scholar
  73. 73.
    Fleming RV, Kantarjian HM, Husni R, Rolston K, Lim J, Raad I, Pierce S, Cortes J, Estey E (2001) Comparison of amphotericin B lipid complex (ABLC) vs. ambisome in the treatment of suspected or documented fungal infections in patients with leukemia. Leuk Lymphoma 40:511–520PubMedCrossRefGoogle Scholar
  74. 74.
    Cannon JP, Garey KW, Danziger LH (2001) A prospective and retrospective analysis of the nephrotoxicity and efficacy of lipid-based amphotericin B formulations. Pharmacotherapy 21:1107–1114PubMedCrossRefGoogle Scholar
  75. 75.
    Mattiuzzi GN, Kantarjian H, Faderl S, Lim J, Kontoyiannis D, Thomas D, Wierda W, Raad I, Garcia-Manero G, Zhou X, Ferrajoli A, Bekele N, Estey E (2004) Amphotericin B lipid complex as prophylaxis of invasive fungal infections in patients with acute myelogenous leukemia and myelodysplastic syndrome undergoing induction chemotherapy. Cancer 100:581–589PubMedCrossRefGoogle Scholar
  76. 76.
    Hachem RY, Boktour MR, Hanna HA, Husni RN, Torres HA, Afif C, Kontoyiannis DP, Raad II (2008) Amphotericin B lipid complex versus liposomal amphotericin B monotherapy for invasive aspergillosis in patients with hematologic malignancy. Cancer 112:1282–1287PubMedCrossRefGoogle Scholar
  77. 77.
    Costa S, Nucci M (2001) Can we decrease amphotericin nephrotoxicity? Curr Opin Crit Care 7:379–383PubMedCrossRefGoogle Scholar
  78. 78.
    Johansen HK, Gotzsche PC (2000) Amphotericin B lipid soluble formulations vs amphotericin B in cancer patients with neutropenia. Cochrane Database Syst Rev 2000(3):CD000969Google Scholar
  79. 79.
    Macauly SS, Martin JE, Zarnke KB (2002) Amphotericin B for the treatment of systemic fungal infections: meta-analysis of conventional versus lipid formulations. In: Interscience Conf on Antimicrobial Agents and Chemotherapy. 42nd ICAAC, San Diego, CA, Abstract —888Google Scholar
  80. 80.
    Barrett JP, Vardulaki KA, Conlon C, Cooke J, Daza-Ramirez P, Evans EG, Hawkey PM, Herbrecht R, Marks DI, Moraleda JM, Park GR, Senn SJ, Viscoli C, Amphotericin B Systematic Review Study Group (2003) A systematic review of the antifungal effectiveness and tolerability of amphotericin B formulations. Clin Ther 25:1295–1320PubMedCrossRefGoogle Scholar
  81. 81.
    Martino R (2004) Efficacy, safety and cost-effectiveness of Amphotericin B Lipid Complex (ABLC): a review of the literature. Curr Med Res Opin 20:485–504PubMedCrossRefGoogle Scholar
  82. 82.
    Moen MD, Lyseng-Williamson KA, Scott LJ (2009) Liposomal amphotericin B: a review of its use as empirical therapy in febrile neutropenia and in the treatment of invasive fungal infections. Drugs 69:361–392PubMedCrossRefGoogle Scholar
  83. 83.
    Safdar A, Ma J, Saliba F, Dupont B, Wingard JR, Hachem RY, Mattiuzzi GN, Chandrasekar PH, Kontoyiannis DP, Rolston KV, Walsh TJ, Champlin RE, Raad II (2010) Drug-induced nephrotoxicity caused by amphotericin B lipid complex and liposomal amphotericin B: a review and meta-analysis. Medicine 89:236–244PubMedCrossRefGoogle Scholar
  84. 84.
    Wong-Beringer A, Jacobs RA, Guglielmo BJ (1998) Lipid formulations of amphotericin B: clinical efficacy and toxicities. Clin Infect Dis 27:603–618PubMedCrossRefGoogle Scholar
  85. 85.
    Matot I, Pizov R (2000) Pulmonary extraction and accumulation of lipid formulations of amphotericin B. Crit Care Med 28:2528–2532PubMedCrossRefGoogle Scholar
  86. 86.
    Hovsepian M, Lee P, Goldstein B (1999) Comparison of safety and cost-effectiveness of Abelcet and Amphotec. American Society of Hospital Pharmacists, Las VegasGoogle Scholar
  87. 87.
    Greenberg RN, Cagnoni PJ, Prendergast MM, Tong KB (2000) Pharmacoeconomics of liposomal amphotericin B versus amphotericin B lipid complex in the empirical treatment of persistently febrile neutropenic patients. In: Interscience Conf on Antimicrobial Agents and Chemotherapy. 40th ICAAC, Toronto, CA, Abstract—506Google Scholar
  88. 88.
    Osswald H, Nabakowski G, Hermes H (1980) Adenosine as a possible mediator of metabolic control of glomerular filtration rate. Int J Biochem 12:263–267PubMedCrossRefGoogle Scholar
  89. 89.
    Gerkens JF, Heidemann HT, Jackson EK, Branch RA (1983) Effect of aminophylline on amphotericin B nephrotoxicity in the dog. J Pharmacol Exp Ther 224:609–613PubMedGoogle Scholar
  90. 90.
    Heidemann HT, Gerkens JF, Jackson EK, Branch RA (1983) Effect of aminophylline on renal vasoconstriction produced by amphotericin B in the rat. Naunyn Schmiedebergs Arch Pharmacol 324:148–152PubMedCrossRefGoogle Scholar
  91. 91.
    Kuan CJ, Branch RA, Jackson EK (1990) Effect of an adenosine receptor antagonist on acute amphotericin B nephrotoxicity. Eur J Pharmacol 178:285–291PubMedCrossRefGoogle Scholar
  92. 92.
    Brooks DP, Mitchell MP, Short BG, Ruffolo RR Jr, Nichols AJ (1991) Attenuation of amphotericin B nephrotoxicity in the dog by the fenoldopam prodrug, SK&F R-105058. J Pharmacol Exp Ther 257:1243–1247PubMedGoogle Scholar
  93. 93.
    Nichols AJ, Koster PF, Brooks DP, Ruffolo RRJR (1992) Effect of fenoldopam on the acute and subacute nephrotoxicity produced by amphotericin B in the dog. J Pharmacol Exp Ther 260:269–274PubMedGoogle Scholar
  94. 94.
    Soupart A, Decaux G (1989) Nifedipine and amphotericin B nephrotoxicity in the rat. Nephron 52:278–280PubMedCrossRefGoogle Scholar
  95. 95.
    Zager RA, Bredl CR, Schimpf BA (1992) Direct amphotericin B-mediated tubular toxicity: assessments of selected cytoprotective agents. Kidney Int 41:1588–1594PubMedCrossRefGoogle Scholar
  96. 96.
    Tolins JP, Raij L (1991) Chronic amphotericin B nephrotoxicity in the rat: protective effect of calcium channel blockade. Am Soc Nephrol 2:98–102Google Scholar
  97. 97.
    Varlam DE, Siddiq MM, Parton LA, Rüssmann H (2001) Apoptosis contributes to amphotericin B-induced nephrotoxicity. Antimicrob Agents Chemother 45:679–685PubMedCrossRefGoogle Scholar
  98. 98.
    Sheikh-Hamad D, Timmins K, Jalali Z (1997) Cisplatin-induced renal toxicity: possible reversal by N-acetylcysteine treatment. J Am Soc Nephrol 8:1640–1644PubMedGoogle Scholar
  99. 99.
    Tariq M, Morais C, Sobki S, Al Sulaiman M, Al Khader A (1999) N-acetylcysteine attenuates cyclosporin-induced nephrotoxicity in rats. Nephrol Dial Transplant 14:923–929PubMedCrossRefGoogle Scholar
  100. 100.
    Mazzon E, Britti D, De Sarro A, Caputi AP, Cuzzocrea S (2001) Effect of N-acetylcysteine on gentamicin-mediated nephropathy in rats. Eur J Pharmacol 424:75–83PubMedCrossRefGoogle Scholar
  101. 101.
    Tepel M, van der Giet M, Schwarzfeld C, Laufer U, Liermann D, Zidek W (2000) Prevention of radiographic-contrast-agent-induced reductions in renal function by acetylcysteine. N Engl J Med 343:180–184PubMedCrossRefGoogle Scholar
  102. 102.
    Feldman L, Efrati S, Dishy V, Katchko L, Berman S, Averbukh M, Aladjem M, Averbukh Z, Weissgarten J (2005) N-acetylcysteine ameliorates amphotericin-induced nephropathy in rats. Nephron Physiol 99:23–27CrossRefGoogle Scholar
  103. 103.
    Odabasi Z, Karaalp A, Cermik H, Mohr J, Tigen ET, Koc M, Korten V (2009) Reduction of amphotericin B-induced renal tubular apoptosis by N-acetylcysteine. Antimicrob Agents Chemother 53:3100–3102PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Iman Karimzadeh
    • 1
  • Hossein Khalili
    • 1
  • Shadi Farsaei
    • 1
  • Simin Dashti-Khavidaki
    • 1
  • Mohammad Mahdi Sagheb
    • 2
  1. 1.Department of Clinical Pharmacy, Faculty of PharmacyTehran University of Medical SciencesTehranIran
  2. 2.Department of Internal Medicine and Nephrology Urology Research Center Shiraz University of Medical SciencesShirazIran

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