Skip to main content
SpringerLink
Log in

Polyene Antifungals

  • Chapter
  • First Online:
Drug Dosing in Obesity

  • 827 Accesses

Abstract

Determining the optimal polyene antifungal dosing in obese patients is considered highly challenging. Limited data are available to describe the pharmacokinetics of polyene antifungals in these patients. However, polyene antifungals demonstrate widely variable pharmacokinetics in various clinical conditions. In particular, the two main parameters that define dosing requirements, volume of distribution (V) and clearance, can change significantly in obese patients. Therefore, in the absence of robust data to describe optimal polyene dosing in obesity , dosing guided by therapeutic drug monitoring (TDM) remains the best approach, particularly when aggressive dosing is required in the context of poorly susceptible pathogens. Lean body weight appears to be the preferred weight metric to estimate polyene dosing in obesity, in order to prevent inappropriate excessive doses and subsequent adverse events including nephrotoxicity.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Groll AH, Piscitelli SC, Walsh TJ. Clinical pharmacology of systemic antifungal agents: a comprehensive review of agents in clinical use, current investigational compounds, and putative targets for antifungal drug development. Adv Pharmacol. 1998;44:343–500.

    Article  CAS  PubMed  Google Scholar 

  2. Groll AH, Walsh TJ. Uncommon opportunistic fungi: new nosocomial threats. Clin Microb Infect (the official publication of the European Society of Clinical Microbiology and Infectious Diseases). 2001;7(Suppl 2):8–24.

    Article  CAS  Google Scholar 

  3. Pennington JE, Block ER, Reynolds HY. 5-fluorocytosine and amphotericin B in bronchial secretions. Antimicrob Agents Chemother. 1974;6(3):324–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Lawrence RM, Hoeprich PD, Jagdis FA, Monji N, Huston AC, Schaffner CP. Distribution of doubly radiolabelled amphotericin B methyl ester and amphotericin B in the non-human primate, Macaca mulatta. J Antimicrob Chemother. 1980;6(2):241–9.

    Article  CAS  PubMed  Google Scholar 

  5. Kerr CM, Perfect JR, Craven PC, Jorgensen JH, Drutz DJ, Shelburne JD, et al. Fungal peritonitis in patients on continuous ambulatory peritoneal dialysis. Ann Intern Med. 1983;99(3):334–6.

    Article  CAS  PubMed  Google Scholar 

  6. Christiansen KJ, Bernard EM, Gold JW, Armstrong D. Distribution and activity of amphotericin B in humans. J Infect Dis. 1985;152(5):1037–43.

    Article  CAS  PubMed  Google Scholar 

  7. Collette N, van der Auwera P, Lopez AP, Heymans C, Meunier F. Tissue concentrations and bioactivity of amphotericin B in cancer patients treated with amphotericin B-deoxycholate. Antimicrob Agents Chemother. 1989;33(3):362–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Bindschadler DD, Bennett JE. A pharmacologic guide to the clinical use of amphotericin B. J Infect Dis. 1969;120(4):427–36.

    Article  CAS  PubMed  Google Scholar 

  9. Drutz DJ, Spickard A, Rogers DE, Koenig MG. Treatment of disseminated mycotic infections. A new approach to amphotericin B therapy. Am J Med. 1968;45(3):405–18.

    Article  CAS  PubMed  Google Scholar 

  10. Utz JP, Garriques IL, Sande MA, Warner JF, Mandell GL, McGehee RF, et al. Therapy of cryptococcosis with a combination of flucytosine and amphotericin B. J Infect Dis. 1975;132(4):368–73.

    Article  CAS  PubMed  Google Scholar 

  11. Dugoni BM, Guglielmo BJ, Hollander H. Amphotericin B concentration in cerebrospinal fluid of patients with AIDS and cryptococcal meningitis. Clin Pharm. 1989;8(3):220–1.

    CAS  PubMed  Google Scholar 

  12. Block ER, Bennett JE, Livoti LG, Klein WJ Jr, MacGregor RR, Henderson L. Flucytosine and amphotericin B: hemodialysis effects on the plasma concentration and clearance. Studies in man. Ann Intern Med. 1974;80(5):613–7.

    Article  CAS  PubMed  Google Scholar 

  13. Morgan DJ, Ching MS, Raymond K, Bury RW, Mashford ML, Kong B, et al. Elimination of amphotericin B in impaired renal function. Clin Pharmacol Ther. 1983;34(2):248–53.

    Article  CAS  PubMed  Google Scholar 

  14. Daneshmend TK, Warnock DW. Clinical pharmacokinetics of systemic antifungal drugs. Clin Pharmacokinet. 1983;8(1):17–42.

    Article  CAS  PubMed  Google Scholar 

  15. Atkinson AJ Jr, Bennett JE. Amphotericin B pharmacokinetics in humans. Antimicrob Agents Chemother. 1978;13(2):271–6.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Hamill RJ. Amphotericin B formulations: a comparative review of efficacy and toxicity. Drugs. 2013;73(9):919–34.

    Article  CAS  PubMed  Google Scholar 

  17. Klepser ME, Wolfe EJ, Jones RN, Nightingale CH, Pfaller MA. Antifungal pharmacodynamic characteristics of fluconazole and amphotericin B tested against Candida albicans. Antimicrob Agents Chemother. 1997;41(6):1392–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Klepser ME, Wolfe EJ, Pfaller MA. Antifungal pharmacodynamic characteristics of fluconazole and amphotericin B against Cryptococcus neoformans. J Antimicrob Chemother. 1998;41(3):397–401.

    Article  CAS  PubMed  Google Scholar 

  19. Turnidge JD, Gudmundsson S, Vogelman B, Craig WA. The postantibiotic effect of antifungal agents against common pathogenic yeasts. J Antimicrob Chemother. 1994;34(1):83–92.

    Article  CAS  PubMed  Google Scholar 

  20. Andes D, Stamsted T, Conklin R. Pharmacodynamics of amphotericin B in a neutropenic-mouse disseminated-candidiasis model. Antimicrob Agents Chemother. 2001;45(3):922–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Vadiei K, Lopez-Berestein G, Luke DR. Disposition and toxicity of amphotericin-B in the hyperlipidemic Zucker rat model. Int J Obes. 1990;14(6):465–72.

    CAS  PubMed  Google Scholar 

  22. Ramaswamy M, Peteherych KD, Kennedy AL, Wasan KM. Amphotericin B lipid complex or amphotericin B multiple-dose administration to rabbits with elevated plasma cholesterol levels: pharmacokinetics in plasma and blood, plasma lipoprotein levels, distribution in tissues, and renal toxicities. Antimicrob Agents Chemother. 2001;45(4):1184–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Ayestaran A, Lopez RM, Montoro JB, Estibalez A, Pou L, Julia A, et al. Pharmacokinetics of conventional formulation versus fat emulsion formulation of amphotericin B in a group of patients with neutropenia. Antimicrob Agents Chemother. 1996;40(3):609–12.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Amantea MA, Bowden RA, Forrest A, Working PK, Newman MS, Mamelok RD. Population pharmacokinetics and renal function-sparing effects of amphotericin B colloidal dispersion in patients receiving bone marrow transplants. Antimicrob Agents Chemother. 1995;39(9):2042–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Heinemann V, Bosse D, Jehn U, Kahny B, Wachholz K, Debus A, et al. Pharmacokinetics of liposomal amphotericin B (Ambisome) in critically ill patients. Antimicrob Agents Chemother. 1997;41(6):1275–80.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Malone ME, Corrigan OI, Kavanagh PV, Gowing C, Donnelly M, D’Arcy DM. Pharmacokinetics of amphotericin B lipid complex in critically ill patients undergoing continuous venovenous haemodiafiltration. Int J Antimicrob Agents. 2013;42(4):335–42.

    Article  CAS  PubMed  Google Scholar 

  27. Roberts JA, Lipman J. Antibacterial dosing in intensive care: pharmacokinetics, degree of disease and pharmacodynamics of sepsis. Clin Pharmacokinet. 2006;45(8):755–73.

    Article  CAS  PubMed  Google Scholar 

  28. Varghese JM, Roberts JA, Lipman J. Antimicrobial pharmacokinetic and pharmacodynamic issues in the critically ill with severe sepsis and septic shock. Crit Care Clin. 2011;27(1):19–34.

    Article  CAS  PubMed  Google Scholar 

  29. Bellmann R, Egger P, Djanani A, Wiedermann CJ. Pharmacokinetics of amphotericin B lipid complex in critically ill patients on continuous veno-venous haemofiltration. Int J Antimicrob Agents. 2004;23(1):80–3.

    Article  CAS  PubMed  Google Scholar 

  30. Bellmann R, Egger P, Gritsch W, Bellmann-Weiler R, Joannidis M, Kaneider N, et al. Amphotericin B lipid formulations in critically ill patients on continuous veno-venous haemofiltration. J Antimicrob Chemother. 2003;51(3):671–81.

    Article  CAS  PubMed  Google Scholar 

  31. Groll AH, Mickiene D, Piscitelli SC, et al. Distribution of lipid formulations of amphotericin B into bone marrow and fat tissue in rabbits. Antimicrob Agents Chemother. 2000;44:408–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Adedoyin A, Bernardo JF, Swenson CE, Bolsack LE, Horwith G, DeWit S, et al. Pharmacokinetic profile of ABELCET (amphotericin B lipid complex injection): combined experience from phase I and phase II studies. Antimicrob Agents Chemother. 1997;41(10):2201–8.

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, QLD, Australia

    Janattul-Ain Jamal & Jason A Roberts

  2. Department of Intensive Care Medicine, Royal Brisbane and Women’s Hospital, Butterfield St., Herston, Brisbane, QLD, 4006, Australia

    Jason A Roberts

  3. Pharmacy Department, Royal Brisbane and Women’s Hospital, Butterfield St., Herston, Brisbane, QLD, 4006, Australia

    Jason A Roberts

  4. School of Pharmacy, The University of Queensland, Brisbane, QLD, Australia

    Jason A Roberts

Authors
  1. Janattul-Ain Jamal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jason A Roberts
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jason A Roberts .

Editor information

Editors and Affiliations

  1. Division of Pharmacy, School of Medicine, University of Tasmania School of Medicine, Hobart, Tasmania, Australia

    Syed Tabish R. Zaidi

  2. School of Medicine and School of Pharmacy, Burns, Trauma and Critical Care Res Cntr, University of Queensland Burns, Trauma and Critical Care Res Cntr, Brisbane, Queensland, Australia

    Jason A. Roberts

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Jamal, JA., Roberts, J.A. (2016). Polyene Antifungals. In: Zaidi, S., Roberts, J. (eds) Drug Dosing in Obesity. Springer, Cham. https://doi.org/10.1007/978-3-319-44034-7_10

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-44034-7_10

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-44032-3

  • Online ISBN: 978-3-319-44034-7

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation