Key result
Orally administered favipiravir reached the cerebrospinal fluid in two patients with BoDV-1 encephalitis, but the half-maximal inhibitory concentration was only met in one patient, suggesting standard dosing may be insufficient.
Why the study?
Borna disease virus 1 causes severe encephalitis with high fatality and lacking treatment recommendations, while little is known about experimental favipiravir pharmacokinetics in encephalitis.
Does orally administered favipiravir reach therapeutic concentrations in the CSF of patients with BoDV-1 encephalitis?
Case Report (n=2)
Yes
Does orally administered favipiravir reach therapeutic concentrations in the CSF of patients with BoDV-1 encephalitis?
Orally administered favipiravir penetrates the CSF in BoDV-1 encephalitis, but current dosing may be insufficient to consistently reach therapeutic antiviral concentrations.
Favipiravir CSF penetration appears inconsistent at standard doses in BoDV-1 encephalitis; leaves open dose-optimization trials before clinical consideration.
BACKGROUND: The Borna disease virus 1 (BoDV-1) causes a rare, but severe form of encephalitis in Germany, characterized by rapid progression, late diagnosis, and a high case fatality. Therapy is experimental and recommendations are lacking. Favipiravir (FPV) suppresses BoDV-1 replication in vitro and has been used in a handful of BoDV-1 patients within individual treatment attempts, but little is known about the drug´s pharmacokinetics in encephalitis. METHODS: To monitor and therefore optimize experimental FPV treatment, we established a liquid chromatography tandem mass spectroscopy (LC-MS/MS) assay for serum and cerebrospinal fluid (CSF), and analyzed stored specimens of two patients with BoDV-1 encephalitis in the context of therapeutic drug monitoring as a pilot investigation. RESULTS: We demonstrate for the first time that orally administered FPV reaches the CSF in BoDV-1 encephalitis. However, the half-maximal inhibitory concentration (IC50) for BoDV-1 was met only in one patient, raising questions on significantly higher dosing and/or alternative formulations for effective treatment. CONCLUSION: In conclusion, monitoring experimental FPV therapy in BoDV-1 encephalitis is feasible and should be performed continuously. Future prospective in-depth (multicenter) studies should include more patients and focus on dose-finding, dose-response relationships, and define a therapeutic index to improve outcomes of this so far nearly uniformly fatal disease.
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Paal et al. (2025) conducted a case report in Borna disease virus 1 (BoDV-1) encephalitis (n=2). Favipiravir was evaluated on Favipiravir concentration in cerebrospinal fluid (CSF). Orally administered favipiravir reached the cerebrospinal fluid in two patients with BoDV-1 encephalitis, but the half-maximal inhibitory concentration was only met in one patient, suggesting standard dosing may be insufficient.
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