ArticleThe Journal of antimicrobial chemotherapy2023
Population pharmacokinetics and CSF penetration of flucytosine in adults with HIV-associated cryptococcal meningoencephalitis.
Article in The Journal of antimicrobial chemotherapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 11 citations in OpenAlex.
- Evaluating the Use of Lower Dose Flucytosine for the Treatment of Cryptococcal Meningitis: A Clinical Trial.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2026Trial
- Use of Isavuconazole in the Treatment of Cryptococcosis: A Real-World Case Series.Infectious diseases and therapy · 2026Article
- In vitro evidence to support amphotericin B and flucytosine combination therapy for talaromycosis.PLoS neglected tropical diseases · 2025Article
- In Vitro Evidence to Support Amphotericin B and Flucytosine Combination Therapy for Talaromycosis.bioRxiv : the preprint server for biology · 2025Article
- Relative Contribution of Pharmacokinetics and Immune Signatures to Clinical Outcomes in Patients With HIV-associated Cryptococcal Meningitis.Open forum infectious diseases · 2025Article
- Evolution of Laboratory Diagnostics for Cryptococcosis and Missing Links to Optimize Diagnosis and Outcomes in Resource-Constrained Settings.Open forum infectious diseases · 2024Review
- 5-Flucytosine Longitudinal Antifungal Susceptibility Testing ofOpen forum infectious diseases · 2023Article
- Challenges and advances in the medical treatment of granulomatous amebic encephalitis.Therapeutic advances in infectious diseaseReview
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Authors and funding
17 authors at 6 institutions in 3 countries.
Funding
Abstract
backgroundThere are limited data describing clinical flucytosine pharmacokinetics (PK). The variability of flucytosine partitioning into the CNS is not known. We described the interindividual variability in flucytosine PK in patients with HIV-associated cryptococcal meningoencephalitis. In addition, we quantified the extent and variability of CSF partitioning of flucytosine.
methodsA PK study was conducted in 64 patients with confirmed HIV-associated cryptococcal meningoencephalitis in Blantyre, Malawi. A four-compartment PK model was developed, and Monte Carlo simulations were performed with flucytosine administered at different doses and in different schedules.
resultsThe estimated mean apparent volume of the central compartment was 17.50 (SD 9.99) L; mean apparent clearance was 5.88 (SD 3.35) L/h; mean apparent volume of the CNS compartment was 41.73 (SD 13.66) L. From the Bayesian posterior estimates, AUC24 values at steady state (144-168 h) with doses of 25 mg/kg q6h were median (IQR) 890.38 (603.81-1213.70) mg.h/L in plasma and 595.66 (425.69-776.64) mg.h/L in CSF. The ratio of CSF:plasma AUC24 was 0.69 (IQR 0.58-0.82).
conclusionsThis study revealed significant interindividual variability in flucytosine PK in plasma and CSF in patients with HIV-associated cryptococcal meningoencephalitis. The population PK model is a first critical step for revised flucytosine regimens that maximize fungal killing and minimize toxicity and the emergence of resistance.
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