| Title: |
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 |
| Authors: |
Michael Paal; Katharina Habler; Alice Ewert; Michael Vogeser; Leonie Grosse; Victoria Lieftüchter; Simone C. Tauber; Johannes Schiefer; Petra Allartz; Dennis Tappe; Kirsten Pörtner |
| Source: |
European Journal of Medical Research, Vol 30, Iss 1, Pp 1-9 (2025) |
| Publisher Information: |
BMC, 2025. |
| Publication Year: |
2025 |
| Collection: |
LCC:Medicine |
| Subject Terms: |
Borna disease virus 1 (BoDV-1); Encephalitis; Favipiravir (FPV); Therapeutic drug monitoring (TDM); Liquid chromatography tandem mass spectroscopy (LC–MS/MS); Medicine |
| Description: |
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. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2047-783X |
| Relation: |
https://doaj.org/toc/2047-783X |
| DOI: |
10.1186/s40001-025-03117-x |
| Access URL: |
https://doaj.org/article/b115bbf6ce8a4e8e855d6dfbd69b684c |
| Accession Number: |
edsdoj.b115bbf6ce8a4e8e855d6dfbd69b684c |
| Database: |
Directory of Open Access Journals |