Pharmacokinetics of 18F-labeled fluconazole in healthy human subjects by positron emission tomography
Open accessAbstract
The distribution of fluconazole in tissue of human volunteers was determined by positron emission tomographic scanning over a 2-h period following the infusion of a tracer dose of 18F-fluconazole (5 to 7 mCi) plus 400 mg of unlabeled drug (the standard daily dose of fluconazole). Previous studies have validated this approach for animals. From serial positron emission tomographic imaging and blood sampling, pharmacokinetics of fluconazole in tissue were determined. There was significant distribution of the radiolabeled drug in all organs studied, with nearly constant levels achieved by 1 h. Plateau concentrations of fluconazole in key organs (micrograms per gram) included the following: whole brain, 4.92 +/- 0.17; heart, 6.98 +/- 0.20; lung, 7.81 +/- 0.46; liver, 12.94 +/- 0.24; spleen, 22.96 +/- 2.5; kidney, 11.23 +/- 0.61; prostate, 8.24 +/- 0.58; and blood, 3.76 +/- 0.30. Since levels of fluconazole of > 6 micrograms/g are needed to treat infection with most strains of Candida and levels of > 10 micrograms/g are needed for Cryptococcus neoformans, Coccidioides immitis, and Histoplasma capsulatum, the following predictions can be made. The current standard dose of 400 mg/day should be more than adequate in the treatment of urinary tract and hepatosplenic candidiasis but problematic in the treatment of candidal osteomyelitis, even with the higher levels that develop after multiple doses. Similarly, higher doses should be considered, particularly in immunocompromised patients, with infection with C. neoformans, H. capsulatum, and C. immitis that involves the central nervous and musculoskeletal systems.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Fluconazole reaches a broad range of physiological concentrations throughout the body.
“The most widely prescribed antifungal drug, fluconazole, disseminates rapidly and reaches a wide range of concentrations throughout the body.”
From Antifungal Drug Concentration Impacts the Spectrum of Adaptive Mutations in <i>Candida albicans</i> (2023) · cites this paper as Fischman et al. 1993
Fluconazole concentrations vary between different tissues in the body (1 μg/ml to over 22 μg/ml), with the highest concentration detected in the spleen.
“Additionally, FLC concentrations vary between different tissues in the body (1 μg/ml to over 22 μg/ml), with the highest concentration of FLC being detected in the spleen (Fischman et al. 1993).”
From Antifungal Drug Concentration Impacts the Spectrum of Adaptive Mutations in <i>Candida albicans</i> (2023) · cites this paper as Fischman et al. 1993
Cites
Multiple Range and Multiple F Tests
Duncan, D. B. (1955) · Biometrics · doi:10.2307/3001478 · Cited by 23,446 · see citing works
Saag, M. S., Powderly, W. G., Cloud, G. A., Robinson, P. A., Grieco, M. H., Sharkey, P. K., Thompson, S. E., Sugar, A. M., Tuazon, C. U., Fisher, J. F., et al. (1992) · New England Journal of Medicine · doi:10.1056/nejm199201093260202 · Cited by 625 · see citing works
Azole antifungal agents: Emphasis on new triazoles
Saag, M. S., & Dismukes, W. E. (1988) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.32.1.1 · Cited by 474 · see citing works
Pharmacokinetics and Tissue Penetration of Fluconazole in Humans
Brammer, K. W., Farrow, P. R., & Faulkner, J. K. (1990) · Clinical Infectious Diseases · doi:10.1093/clinids/12.supplement_3.s318 · Cited by 430 · see citing works
Humphrey, M., Jevons, S., & Tarbit, M. H. (1985) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.28.5.648 · Cited by 367 · see citing works
Fluconazole Compared with Amphotericin B plus Flucytosine for Cryptococcal Meningitis in AIDS
Larsen, R. A., Leal, M. A. E., & Chan, L. S. (1990) · Annals of Internal Medicine · doi:10.7326/0003-4819-113-3-183 · Cited by 359 · see citing works
Powderly, W. G., Saag, M. S., Cloud, G. A., Robinson, P. A., Meyer, R. D., Jacobson, J. M., Graybill, J. R., Sugar, A. M., McAuliffe, V. J., Follansbee, S., et al. (1992) · New England Journal of Medicine · doi:10.1056/nejm199203193261203 · Cited by 351 · see citing works
Biochemical Targets for Antifungal Azole Derivatives: Hypothesis on the Mode of Action
Vanden Bossche, H. (1985) · Current Topics in Medical Mycology · doi:10.1007/978-1-4613-9547-8_12 · Cited by 321 · see citing works
In vitro and in vivo effects of the antimycotic drug ketoconazole on sterol synthesis
den Bossche, H. V., Willemsens, G., Cools, W., Cornelissen, F. W., Lauwers, W., & Cutsem, J. M. V. (1980) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.17.6.922 · Cited by 277 · see citing works
Anaissie, E. J., Bodey, G. P., Kantarjian, H. M., David, C. L., Barnett, K., Bow, E. J., DeFelice, R., Downs, N., File, T. M., Karam, G. A., et al. (1991) · The American Journal of Medicine · doi:10.1016/0002-9343(91)90006-j · Cited by 217 · see citing works
Watson, P. F., Rose, M. E., Ellis, S. W., England, H., & Kelly, S. L. (1989) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(89)91792-0 · Cited by 197 · see citing works
Performance Characteristics of an Eight-Ring Whole Body PET Scanner
Kops, E. R., Herzog, H. R., Schmid, A., Holte, S., & Feinendegen, L. E. (1990) · Journal of Computer Assisted Tomography · doi:10.1097/00004728-199005000-00022 · Cited by 194 · see citing works
Hepatosplenic candidiasis: Successful treatment with fluconazole
Kauffman, C. A., Bradley, S., Ross, S. C., & Weber, D. R. (1991) · The American Journal of Medicine · doi:10.1016/0002-9343(91)90005-i · Cited by 193 · see citing works
Activity of fluconazole (UK 49,858) and ketoconazole against Candida albicans in vitro and in vivo
Rogers, T. E., & Galgiani, J. N. (1986) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.30.3.418 · Cited by 184 · see citing works
den Bossche, H. V., Willemsens, G., Cools, W., Marichal, P., & Lauwers, W. (1983) · Biochemical Society Transactions · doi:10.1042/bst0110665 · Cited by 173 · see citing works
Arndt, C. A. S., Walsh, T. J., McCully, C. L., Balis, F. M., Pizzo, P. A., & Poplack, D. G. (1988) · The Journal of Infectious Diseases · doi:10.1093/infdis/157.1.178 · Cited by 169 · see citing works
Discovery of Fluconazole, a Novel Antifungal Agent
Richardson, K., Cooper, K., Marriott, M. S., Tarbit, M. H., Troke, F., & WHITTLE, P. J. (1990) · Clinical Infectious Diseases · doi:10.1093/clinids/12.supplement_3.s267 · Cited by 136 · see citing works
Fluconazole Penetration into Cerebrospinal Fluid in Humans
Foulds, G. H., Brennan, D. R., Wajszczuk, C. P., Catanzaro, A., Garg, D. C., Knopf, W. D., Rinaldi, M. G., & Weidler, D. J. (1988) · The Journal of Clinical Pharmacology · doi:10.1002/j.1552-4604.1988.tb03159.x · Cited by 121 · see citing works
Use of high-dose fluconazole as salvage therapy for cryptococcal meningitis in patients with AIDS
Berry, A. J., Rinaldi, M. G., & Graybill, J. R. (1992) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.36.3.690 · Cited by 80 · see citing works
Pharmacokinetics and tissue penetration of fluconazole in rabbits
Walsh, T. J., Foulds, G. H., & Pizzo, P. A. (1989) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.33.4.467 · Cited by 72 · see citing works
Successful treatment of invasive fungal infection with fluconazole in organ transplant recipients.
Conti, D. J., TOLKOFF-RUBIN, N. E., Gp, B., Doran, M. T., COSIMI, A. B., Delmonico, F. L., Auchincloss, H., Russell, P. S., & Rubin, R. H. (1989) · PubMed · Cited by 57 · see citing works
Self-citationToxicological Profile and Safety Evaluation of Antifungal Azole Derivatives
Cauteren, H. V., Lampo, A., Vandenberghe, J., Vanparys, P., Coussement, W., Coster, R. D., & Marsboom, R. (1989) · Mycoses · doi:10.1111/j.1439-0507.1989.tb02295.x · Cited by 52 · see citing works
Hughes, C. E., Bennett, R. L., Tuna, I. C., & Beggs, W. H. (1988) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.32.2.209 · Cited by 49 · see citing works
Design and Evaluation of a Systemically Active Agent, Fluconazole
Richardson, K., Cooper, K., Marriott, M. S., et al. (1988) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1988.tb40385.x · Cited by 45 · see citing works
Steady State Parenteral Kinetics of Fluconazole in Man
Foulds, G. H., Wajszczuk, C. P., Weidler, D. J., Garg, D., & GIBSON, P. (1988) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1988.tb40440.x · Cited by 41 · see citing works
Debruyne, D., Ryckelynck, J. P., Bigot, M.-C., et al. (1988) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.2600770615 · Cited by 36 · see citing works
Fischman, A. J., Alpert, N. M., Livni, E., et al. (1991) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)20553-5 · Cited by 34 · see citing works
Self-citationLarsen, R. A. (1990) · The Journal of Infectious Diseases · doi:10.1093/infdis/162.3.727 · Cited by 34 · see citing works
Sputum levels of fluconazole in humans
Ebden, P., Neill, P., & Farrow, P. R. (1989) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.33.6.963 · Cited by 33 · see citing works
The Discovery and Profile of Fluconazole
Richardson, K. (1990) · Journal of Chemotherapy · doi:10.1080/1120009x.1990.11738981 · Cited by 32 · see citing works
Synthesis of 18F-labeled fluconazole and positron emission tomography studies in rabbits
Livni, E., Fischman, A. J., Ray, S. J., et al. (1992) · International Journal of Radiation Applications and Instrumentation Part B Nuclear Medicine and Biology · doi:10.1016/0883-2897(92)90007-l · Cited by 25 · see citing works
Self-citationThe average density of healthy lung.
Jf, F., & Ae, Y. (1959) · PubMed · Cited by 17 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Antifungal Drug Concentration Impacts the Spectrum of Adaptive Mutations in <i>Candida albicans</i>
Todd, R. T., Soisangwan, N., Peters, S., Kemp, B., Crooks, T., Gerstein, A., & Selmecki, A. (2023) · Molecular Biology and Evolution · doi:10.1093/molbev/msad009 · Cited by 53 · see citing works
- Authors
- Fischman, A. J., Alpert, N. M., Livni, E., Ray, S., Sinclair, I., Callahan, R. J., Correia, J. A., Webb, D., Strauss, H. W., & Rubin, R. H.
- Affiliations
- Massachusetts General Hospital (US)
- Department of Radiology, Massachusetts General Hospital, Boston 02114.
- ORCID
- Venue
- Antimicrobial Agents and Chemotherapy
- Publisher
- American Society for Microbiology
- Published
- 1993-06
- Volume
- 37
- Issue
- 6
- Pages
- 1270-1277
- ISSN
- 0066-4804 (ISSN-L)
- 1098-6596
- PMC
- PMC187952
- OpenAlex
- W2076134038
- Cited by
- 93
- References
- 32
- Citations by year
- 2024: 3 · 2023: 1 · 2022: 1 · 2021: 6 · 2020: 1 · 2019: 4 · 2018: 5 · 2017: 3 · 2015: 1 · 2014: 2 · 2013: 2 · 2012: 2
- FWCI
- 3.40
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Antimicrobial Agents and Chemotherapy (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Pfizer
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Health Sciences › Medicine › Pharmacology › Antibiotics Pharmacokinetics and Efficacy
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Keywords
- fluconazole, pharmacokinetics, tissue distribution, radiolabeled drug, antifungal agents, Candida, Cryptococcus neoformans, Coccidioides immitis, Histoplasma capsulatum, candidiasis, dose optimization, immunocompromised patients, positron emission tomography
- MeSH terms
- Adult, Brain, Fluorine Radioisotopes, Humans, Male, Tissue Distribution, Tomography, Emission-Computed, Fluconazole
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
