First therapeutic drug monitoring of experimental favipiravir in Borna disease virus 1 (BoDV-1) encephalitis patients reveals significant gaps in antiviral treatment: a pilot investigation
First therapeutic drug monitoring of experimental favipiravir in Borna disease virus 1 (BoDV-1) encephalitis patients reveals significant gaps in antiviral treatment: a pilot investigation

First therapeutic drug monitoring of experimental favipiravir in Borna disease virus 1 (BoDV-1) encephalitis patients reveals significant gaps in antiviral treatment: a pilot investigation

Eur J Med Res. 2025 Oct 4;30(1):928. doi: 10.1186/s40001-025-03117-x.

ABSTRACT

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.

PMID:41046256 | DOI:10.1186/s40001-025-03117-x