Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Current Fungal Infection Reports
Published in: Current Fungal Infection Reports 2/2011

01-06-2011

Antifungal Dosing in Obesity: A Review of the Literature

Authors: Jarrett R. Amsden, Douglas Slain

Published in: Current Fungal Infection Reports | Issue 2/2011

Login to get access

Abstract

Obesity is becoming a global pandemic that is projected to increase significantly over the next few decades. Unfortunately, studies of drug dosing and pharmacokinetics have largely excluded obese patients. Currently, literature inadequately characterizes drug disposition in these patients. Only a limited selection of literature addresses antibacterial dosing in obesity, and virtually none characterizes antifungal dosing in obesity. This review discusses the changes in pharmacokinetics that occur in obesity and the available in vitro and in vivo data describing the disposition of antifungal agents in obese animals and patients.
Literature
1.
2.
Wang Y, Beydoun MA, Liang L, Caballero B, Kumanyika SK. Will all Americans become overweight or obese? Estimating the progression and cost of the US obesity epidemic. Obesity. 2008;16:2323–30.PubMedCrossRef
3.
4.
Cheymol G. Effects of obesity on pharmacokinetics: implications for drug therapy. Clin Pharmacokinet. 2000;39:215–31.PubMedCrossRef
5.
• Hanley MJ, Abernathy DR, Greenblatt DJ. Effect of obesity on the pharmacokinetics of drugs in humans. Clin Pharmacokinet. 2010;49:71–87. This review is the most recent update of the effects of obesity on human pharmacokinetics. The authors provide a thorough discussion of the different derivations of weight descriptors and their utility. This article also provides complete descriptions of drug disposition: volume of distribution, clearance, half-life, and the variations of these parameters in obese patients. It also thoroughly reviews the available literature on dosing of individual drugs and drug classes in obese patients. PubMedCrossRef
6.
Wurtz R, Itokazu G, Rodvold K. Antimicrobial dosing in obesity. Clin Infect Dis. 1999;25:112–8.CrossRef
7.
Bearden DT, Rodvold KA. Dosage adjustments for antibacterials in obese patients: applying clinical pharmacokinetics. Clin Pharmacokinet. 2000;38:415–26.PubMedCrossRef
8.
Erstad BL. Dosing of medications in morbidly obese patients in the intensive care unit setting. Intensive Care Med. 2004;30:18–32.PubMedCrossRef
9.
Pai MP, Bearden DT. Antimicrobial dosing considerations in obese adult patients. Pharmacotherapy. 2007;27:1081–91.PubMedCrossRef
10.
Devine D. Case Study Number 25 Gentamicin Therapy. Drug Intell Clin Pharm. 1974;8:650–5.
11.
12.
Cheng P-Y, Morgan ET. Hepatic cytochrome P450 regulation in disease states. Curr Drug Metab. 2001;2:165–83.PubMedCrossRef
13.
Janmahasatian S, Dufffull SB, Ash S, Ward LC, Byrne NM, Green B. Quantification of lean body weight. Clin Pharmacokinet. 2005;44:1051–65.PubMedCrossRef
14.
Han PY, Duffull SB, Kirkpatrick CMJ, Green B. Dosing in obesity: a simple solution to a big problem. Clin Pharmacol Ther. 2007;82:505–8.PubMedCrossRef
15.
• Pai MP. Estimating the glomerular filtration rate in obese adult patients for drug dosing. Adv Chronic Kidney Dis. 2010;5:e53-e62. This article thoroughly reviews the effect of obesity on GFR. The author reviews the derivations of the various GFR equations, Cockcroft and Gault, and their limitations in predicting GFR and creatinine clearance. He compares and contrasts the ability of calculated weight descriptors to predict GFR and provides the equations for each. Finally, he concludes with practical considerations for using our current GFR and creatinine clearance calculations and proposes the use of other weight descriptors in these equations to improve clinical estimates. CrossRef
16.
Slain D. Lipid-based amphotericin B for the treatment of fungal infections. Pharmacotherapy. 1999;19:306–23.PubMedCrossRef
17.
Atkinson AJ, Bennett JE. Amphotericin B pharmacokinetics in humans. Antimicrob Agents Chemother. 1978;13:271–6.PubMed
18.
Janknegt R, de Marie S, Bakker-Woudenberg IA, et al. Liposomal and lipid formulations of amphotericin B: clinical pharmacokinetics. Clin Pharmacokinet. 1992;23:279–91.PubMedCrossRef
19.
Daneshmend TK, Warnock DW. Clinical pharmacokinetics of systemic antifungal drugs. Clin Pharmacokinet. 1983;8:17–42.PubMedCrossRef
20.
Brajtburg J, Elberg S, Bolard J, et al. Interaction of plasma proteins and lipoproteins with amphotericin B. J Infect Dis. 1984;149:986–97.PubMedCrossRef
21.
Collette N, Van der Auwera P, Van der Pascual Lopez A, et al. Tissue concentrations and bioactivity of amphotericin B in cancer patients treated with amphotericin B deoxycholate. Antimicrob Agents Chemother. 1989;33:362–8.PubMed
22.
Craven PC, Ludden TM, Drutz DJ, et al. Excretion pathways of amphotericin B. J Infect Dis. 1979;140:329–41.PubMedCrossRef
23.
Walsh TJ, Goodman JL, Pappas P, Bekersky I, Buell DN, Roden M, et al. Safety, tolerance, and pharmacokinetics of high-dose liposomal amphotericin B (AmBisome) in patients infected with Aspergillus species and other filamentous fungi: maximum tolerated dose study. Antimicrob Agents Chemother. 2001;45:3487–96.PubMedCrossRef
24.
Gallis HA, Drew RH, Pichard WW. Amphotericin B 30 years of clinical experience. Rev Infect Dis. 1990;12:308–29.PubMedCrossRef
25.
Christiansen KJ, Bernard EM, Gold JWM, et al. Distribution and activity of amphotericin B in humans. J Infect Dis. 1985;152:1037–43.PubMedCrossRef
26.
Vadiei K, Lopez-Berestein G, Luke DR. Disposition and toxicity of amphotericin B in the hyperlipidemic Zucker Rat Model. Int J Obes. 1990;14:465–72.PubMed
27.
Ramaswamy M, Peteherych KD, Kennedy AL, et al. 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;45:1184–91.PubMedCrossRef
28.
Brown CD, Higgins M, Donato KA, et al. Body mass index and the prevalence of hypertension and dyslipidemia. Obes Res. 2000;8:605–19.PubMedCrossRef
29.
Koldin MH, Kobayashi GS, Brajtburg, et al. Effects of elevation of serum cholesterol and administration of amphotericin B complexed to lipoproteins on amphotericin B-induced toxicity in rabbits. Antimicrob Agents Chemother. 1985;28:144–5.PubMed
30.
Wasan KM, Kennedy AL, Cassidy SM, et al. Pharmacokinetics, distribution in serum lipoproteins and tissues, and renal toxicities of amphotericin B and amphotericin B lipid complex in a hypercholesterolemic rabbit model: Single-dose studies. Antimicrob Agents Chemother. 1998;42:3146–52.PubMed
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.PubMedCrossRef
32.
Collette N, Van der Auwera P, Meunier F, et al. Tissue distribution and bioactivity of amphotericin B administration in liposomes to cancer patients. J Antimicrob Chemother. 1991;27:535–48.PubMedCrossRef
33.
Bellmann R. Clinical pharmacokinetics of systemically administered antimycotics. Curr Clin Pharmacol. 2007;2:37–58.PubMedCrossRef
34.
35.
Theuretzbacher U, Ihle F, Derendorf H. Pharmacokinetic/pharmacodynamic profile of voriconazole. Clin Pharmacokinet. 2006;45:649–63.PubMedCrossRef
36.
Li Y, Theuretzbacher U, Clancy CJ, Nguyen MH, Derendorf H. Pharmacokinetic/pharmacodynamic profile of posaconazole. Clin Pharmacokinet. 2010;49:379–96.PubMedCrossRef
37.
Glassner-Cohen L, DiBiasio A, Lisco SJ, Hurford WE. Fluconazole serum concentrations and pharmacokinetics in an obese patient. Pharmacotherapy. 1997;17:1023–6.
38.
Anaissie EJ, Kontoyiannis DP, Huls C, Vartivarian SE, Karl C, Prince RA, et al. Safety, plasma concentrations, and efficacy of high-dose fluconazole in invasive mold infections. J Infect Dis. 1995;172:599–602.PubMedCrossRef
39.
Wasan KM, Kennedy AL, Cassidy SM, et al. Pharmacokinetics, distribution in serum lipoproteins and tissues, and renal toxicities of amphotericin B and amphotericin B lipid complex in a hypercholesterolemic rabbit model: single-dose studies. Antimicrob Agents Chemother. 1998;42:3146–52.PubMed
40.
• Pai MP, Lodise TP. Pharmacokinetics (PK) of voriconazole (VOR) in obese (OB) adults. Poster A1–044. Presented at the 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); September 12–15, 2010, Boston, MA. Though currently available only in abstract/poster form and described in the article, this is one of the first comparative pharmacokinetic studies describing drug disposition of an antifungal agent (voriconazole) in obese patients. This study compares two different doses of voriconazole in obese patients and in historical, nonobese control patients. The study demonstrates no significant differences in apparent voriconazole pharmacokinetic values between obese and nonobese patients, but differences are noted when adjusted for average TBW. The authors further describe the correlations of TBW and LBW (2005) to AUC values. This article provides some much-needed evidence about the disposition of voriconazole in obese patients.
41.
Estes KE, Penzak SR, Calis KA, et al. Pharmacology and antifungal properties of anidulafungin, A new echinocandin. Pharmacotherapy. 2009;29:17–30.PubMedCrossRef
42.
Gumbo T. Impact of pharmacodynamics and pharmacokinetics on echinocandin dosing strategies. Curr Opin Infect Dis. 2007;20:587–91.PubMedCrossRef
43.
Stone JA, Xu X, Winchell GA, et al. Disposition of caspofungin: role of distribution in determining pharmacokinetics in plasma. Antimicrob Agents Chemother. 2004;48:815–23.PubMedCrossRef
44.
Damle B, Stogniew M, Dowell J. Pharmacokinetics and tissue distribution of anidulafungin in rats. Antimicrob Agents Chemother. 2008;52:2673–6.PubMedCrossRef
45.
Groll AH, Mickiene D, Petraitis V, et al. Compartmental pharmacokinetics and tissue distribution of the antifungal echinocandin lipopeptide micafungin in rabbits. Antimicrob Agents Chemother. 2001;45:3322–7.PubMedCrossRef
46.
Ryan D, Lupinacci R, Kartsonis N. Efficacy and safety of caspofungin in obese patients [Abstract # 1040] in program and abstracts of the 47th annual meeting of the Infectious Diseases Society of America, October 29–November 1, 2009, Philadelphia, PA.
47.
Stone JA, Winchell GA, Bi S, et al. Population pharmacokinetics of caspofungin in candidiasis patients [abstract A-1571]. Available in program and abstracts of the 43rd Annual Meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy, September 14–17, 2009, Chicago, IL.
48.
Nguyen TH, Hoppe-Tichy T, Geiss HK, et al. Factors influencing caspofungin plasma concentrations in patients of a surgical intensive care unit. J Antimicrob Chemother. 2007;60:100–6.PubMedCrossRef
49.
Gumbo T, Hiemenz J, Ma L, et al. Population pharmacokinetics of micafungin in adult patients. Diagn Microbiol Infect Dis. 2008;60:329–31.PubMedCrossRef
50.
Hebert MF, Smith HE, Marbury TC, et al. Pharmacokinetics of micafungin in healthy volunteers with moderate liver disease, and volunteers with renal dysfunction. J Clin Pharmacol. 2005;45:1145–52.PubMedCrossRef
51.
Dowell JA, Knebel W, Ludden T, et al. Population pharmacokinetic analysis of anidulafungin, an echinocandin antifungal. J Clin Pharmacol. 2004;44:590–8.PubMedCrossRef
52.
Betts RF, Nucci M, Talwar D, et al. A multicenter, double-blind trial of a high-dose caspofungin treatment regimen versus a standard caspofungin treatment regimen for adult patients with invasive candidiasis. Clin Infect Dis. 2009;48:1676–84.PubMedCrossRef
53.
Vermes A, Guchelaar H-J, Dankert J. Flucytosine: a review of its pharmacology, clinical indications, pharmacokinetics, toxicity and drug interactions. J Antimicrob Chemother. 2000;46:171–9.PubMedCrossRef
54.
Gillum JG, Johnson M, Lavoie S, Venitz J. Flucytosine dosing in an obese patient with extrameningeal cryptococcal infection. Pharmacotherapy. 1995;15:251–3.PubMed
Metadata
Title
Antifungal Dosing in Obesity: A Review of the Literature
Authors
Jarrett R. Amsden
Douglas Slain
Publication date
01-06-2011
Publisher
Current Science Inc.
Published in
Current Fungal Infection Reports / Issue 2/2011
Print ISSN: 1936-3761
Electronic ISSN: 1936-377X
DOI
https://doi.org/10.1007/s12281-011-0049-7

Other articles of this Issue 2/2011

Current Fungal Infection Reports 2/2011 Go to the issue

ReviewPaper

Antifungal Therapy in Pediatric Patients

ReviewPaper

Antifungal Dosing in Dialysis and Continuous Renal Replacement Therapy

ReviewPaper

Update on Antifungal Drug Dosing and Therapeutic Drug Monitoring

ReviewPaper

Antifungal Pharmacokinetics and Dosing Considerations in Burn Patients

ReviewPaper

Pros and Cons of Extrapolating Animal Data on Antifungal Pharmacodynamics to Humans

Clinical Trial Report

Optimizing Amphotericin B Therapy for Cryptococcal Meningitis
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits