Fluconazole levels in serum and cerebrospinal fluid according to daily dosage in patients with cryptococcosis and other fungal infections

Schiave, Letícia Aparecida; Nascimento, Erika; Vilar, Fernando Crivelenti; de Haes, Tissiana Marques; Takayanagui, Osvaldo Massaiti; Gaitani, Cristiane Masetto de; Martinez, Roberto

doi:10.1016/j.bjid.2017.10.003

Cited by 15Fungal Infections and StudiesAntifungal resistance and susceptibilityAntibiotics Pharmacokinetics and Efficacy

Fluconazole levels in serum and cerebrospinal fluid according to daily dosage in patients with cryptococcosis and other fungal infections

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Schiave, Letícia Aparecida, Nascimento, Erika, Vilar, Fernando Crivelenti, de Haes, Tissiana Marques, Takayanagui, Osvaldo Massaiti, Gaitani, Cristiane Masetto de, Martinez, Roberto·2018·The Brazilian Journal of Infectious Diseases

DOI 10.1016/j.bjid.2017.10.003PMC PMC9425654

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Abstract

Fluconazole is extensively used for the treatment of candidiasis and cryptococcosis. Among other factors, successful treatment is related to appropriate fluconazole levels in blood and cerebrospinal fluid. In the present study, fluconazole levels were determined in 15 patients, 14 of whom had AIDS and 13 had neurocryptococcosis. The only selection criterion was treatment with fluconazole, which was performed with a generic or similar form of the drug. Fluconazole level was determined by high performance liquid chromatography and the susceptibility profile of Cryptococcus spp. isolated from the patients was assessed by broth microdilution. Blood and cerebrospinal fluid fluconazole levels were found to be related to the fluconazole daily dose, and exceeded the minimum inhibitory concentration of this antifungal for the Cryptococcus spp. isolates. A good correlation was observed between serum and cerebrospinal fluid drug concentration. In conclusion, treatment with non-original fluconazole under usual medical practice conditions results in appropriate blood and cerebrospinal fluid levels of the drug for inhibiting Cryptococcus spp. susceptible to this antifungal drug. The relatively common failures of neurocryptococcosis treatment appear not to be due to insufficient fluconazole levels in the cerebrospinal fluid, especially with the use of daily doses of 400-800mg.

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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 Candida albicans (2023) · cites this paper as Schiave et al. 2018
Serum concentrations of fluconazole are dose-dependent, with typical doses of 200-800 mg/day corresponding to serum concentrations of ∼7.5-60.5 μg/ml.
“Serum concentrations are dose-dependent, with typical doses of 200–800 mg/day FLC corresponding to serum concentrations of ∼7.5–60.5 μg/ml FLC (Schiave et al. 2018).”
From Antifungal Drug Concentration Impacts the Spectrum of Adaptive Mutations in Candida albicans (2023) · cites this paper as Schiave et al. 2018

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Authors: Schiave, L. A., Nascimento, E., Vilar, F. C., de Haes, T. M., Takayanagui, O. M., Gaitani, C. M. D., & Martinez, R.
Affiliations: Universidade de São Paulo (BR)
ORCID: Vilar, Fernando Crivelenti
Takayanagui, Osvaldo Massaiti
Gaitani, Cristiane Masetto de
Venue: The Brazilian Journal of Infectious Diseases
Publisher: Elsevier BV
Published: 2018-01
Volume: 22
Issue: 1
Pages: 11-15
ISSN: 1413-8670 (ISSN-L)
DOI: 10.1016/j.bjid.2017.10.003
PMC: PMC9425654
OpenAlex: W2769484517
Cited by: 15
References: 27
Citations by year: 2026: 2 · 2025: 3 · 2024: 1 · 2023: 4 · 2022: 1 · 2020: 2 · 2019: 1 · 2018: 1
FWCI: 0.86
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by-nc-nd
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by-nc-nd/4.0/ (vor)
Locations: The Brazilian Journal of Infectious Diseases (publishedVersion, cc-by-nc-nd)
PubMed Central (publishedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion, other-oa)
Americanae (AECID Library) (submittedVersion, other-oa)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics: Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
Health Sciences › Medicine › Pharmacology › Antibiotics Pharmacokinetics and Efficacy
Keywords: fluconazole, cryptococcosis, neurocryptococcosis, cerebrospinal fluid drug concentration, serum drug concentration, antifungal dosing, Cryptococcus, AIDS, candidiasis, antifungal susceptibility, treatment failure
MeSH terms: Adult, Antifungal Agents, Candidiasis, Chromatography, High Pressure Liquid, Cryptococcosis, Cryptococcus, Dose-Response Relationship, Drug, Histoplasmosis, Humans, Microbial Sensitivity Tests, Middle Aged, Reference Values, Fluconazole, Treatment Outcome, AIDS-Related Opportunistic Infections, Statistics, Nonparametric

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Fluconazole levels in serum and cerebrospinal fluid according to daily dosage in patients with cryptococcosis and other fungal infections

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