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.
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.
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.
Paal et al. (Sat,) 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.